Substitute diphenylamine compounds use thereof as antitumor agents

ABSTRACT

The invention relates to substituted diphenylamine compounds using as antitumor agents. The structure of the compounds is represented as the general formula (I): 
     
       
         
         
             
             
         
       
     
     The groups are as defined as specification. 
     The compound represented by formula (I) showed potent antitumor activity, especially to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The preferred cancers are: colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx cancer or stomach cancer.

FIELD OF THE INVENTION

The present invention relates to the field of medicine. Specifically toa substituted diphenylamine compounds and uses thereof as antitumoragents.

BACKGROUND OF THE INVENTION

The following compounds, which can be used as intermediates tosynthetise a kind of multi-halogenated acridone compounds havingfluorescence and pharmaceutical activity, were reported in patentCN101391981A. The invention discloses compounds KC1(IV-A), KC2(IV-B),KC3(IV-D), KC4(IV-E), KC5(IV-H) and KC6(IV-C), but there are nobioactivity reported. The compound KC1(XXIX) was also reported inPesticide Science (1988), 24(2), 111-21, showing fungicidal activityagainst grape downy mildew (Plasmopora viticola).

The compounds having the following general formulas were reported asinsecticides, acaricides, fungicides, herbicides, rodenticide or othersin the prior art:

Such as patents BR7900462, CH626323, CN1188757, DE2509416, DE2642147,DE2642148, EP26743, EP60951, GB1544078, GB1525884, JP58113151,JP64001774, JP01186849, WO2002060878, WO2005035498, WO2009037707, U.S.Pat. No. 3,948,957, U.S. Pat. No. 3,948,990, U.S. Pat. No. 4,041,172,U.S. Pat. No. 4,152,460, U.S. Pat. No. 4,187,318, U.S. Pat. No.4,215,145, U.S. Pat. No. 4,304,791, U.S. Pat. No. 4,316,988, U.S. Pat.No. 4,407,820, U.S. Pat. No. 4,459,304, U.S. Pat. No. 4,670,596 and soon, and ACS Symposium Series (1992), 504 (Synth. Chem. Agrochem. III),336-48; Journal of the Chemical Society (1951), 110-15, etc. allreported the compounds having above general formulas.

In addition, the compounds of the following general formulas werementioned in Chemische Berichte (1962), 95 1711-21; Chemische Berichte(1963), 96(7), 1936-44; Journal of Organic Chemistry (1954), 19, 1641-5;Journal of the Chemical Society; Transactions (1913), 103 982-8 andJournal of the Chemical Society, Transactions (1921), 119, 187-92 and soon, but without any bioactivity reported:

The compounds having the following general formulas as fungicide werereported in patent WO2012171484:

The compounds having the following general formulas as fungicide werereported in patent WO2011116671:

The compounds having the structure of general formula I were notreported in the prior art as antitumor agents.

SUMMARY OF THE INVENTION

The object of the present invention is to provide substituteddiphenylamine compounds having general formula I, which can be appliedto antitumor agents.

Detailed description of the invention is as follows:

Substituted diphenylamine compounds use thereof as antitumor agents, thecompounds having the structure of general formula I:

Wherein:

R₁ is selected from H, C₁-C₈alkyl, C₃-C₈cycloalkyl, C₁-C₈haloalkyl,C₁-C₈alkylcarbonyl, C₁-C₈halo alkylcarbonyl, C₁-C₈ alkoxycarbonyl,C₁-C₈alkylamino carbonyl, C₁-C₈alkylthio, C₁-C₈halo alkylthio,C₁-C₈alkylsulfonyl, C₁-C₈ alkoxyC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl,C₁-C₈alkylaminothio, C₂-C₈dialkylaminothio, C₂-C₈ alkenyl, C₂-C₈alkynyl,C₂-C₈haloalkenyl, C₂-C₈haloalkynyl, aryl C₁-C₈alkyl or CO—X—CO₂R₁₂, inwhich X is selected from (CHR₁₂)n, CR₁₂═CR₁₃ or C₆H₄, n=1-6;

R₂ and R₆ may be the same or different, respectively selected from H,halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈halo alkyl,C₁-C₈alkoxy, C₁-C₈halo alkoxy, C₁-C₈alkylthio, C₁-C₈halo alkylthio,C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl,C₁-C₈alkoxycarbonyl, C₁-C₈ alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl, or the following groups unsubstituted orsubstituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy, arylamino,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl orheteroaryloxy, and when the number of the substitutes is more than 1,R₁₄ may be the same or different;

R₃ and R₅ may be the same or different, respectively selected from H,halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈halo alkyl, C₁-C₈alkoxy, C₁-C₈halo alkoxy, C₁-C₈alkylamino, C₁-C₈halo alkylamino,C₁-C₈alkylthio, C₁-C₈halo alkylthio, C₂-C₈alkenyl, C₂-C₈alkynyl,C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl, C₁-C₈ alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkylcarbonyloxy,C₁-C₈ alkoxycarbonyloxy, C₁-C₈alkylaminocarbonyloxy,C₁-C₈alkylsulfonyloxy, C₁-C₈ alkoxyC₁-C₈ alkoxy, C₁-C₈haloalkoxyC₁-C₈halo alkoxy, C₁-C₈ alkoxycarbonylC₁-C₈ alkoxy, or thefollowing groups unsubstituted or substituted with 1-5 R₁₄: aryl,arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl,aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the numberof the substitutes is more than 1, R₁₄ may be the same or different;

R₄ is selected from H, halogen, CN, NO₂, COOH, CO₂Na, CO₂NH₄,C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈halo alkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₁-C₈alkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈ alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈ alkoxy,C₁-C₈haloalkoxyC₁-C₈haloalkoxy, SO₂NR₁₂R₁₃, or the following groupsunsubstituted or substituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy,arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl,arylaminocarbonyl or heteroaryloxy, and when the number of thesubstitutes is more than 1, R₁₄ may be the same or different;

R₇ is selected from Cl or CH₃;

R₈ is selected from H, halogen, OH, CN, NO₂, COOH, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈halo alkoxy, C₁-C₈alkylamino,C₁-C₈halo alkylamino, C₁-C₈alkylthio, C₁-C₈halo alkylthio,C₁-C₈alkylsulfonyl, C₃-C₈ cycloalkyl, C₂-C₈dialkylamino, C₃-C₈alkenyloxy, C₃-C₈haloalkenyloxy, C₃-C₈alkynyloxy, C₃-C₈halo alkynyloxy,C₁-C₈alkylcarbonyloxy, C₁-C₈alkylcarbonylamino, C₁-C₈alkylsulfonyloxy,C₁-C₈ alkoxyC₁-C₈ alkoxy, C₁-C₈ alkoxycarbonylC₁-C₈ alkoxy, or thefollowing groups unsubstituted or substituted with 1-5 R₁₄: aryloxy,arylamino, arylmethoxy, arylmethylamino, heteroaryloxy orheteroarylamino, and when the number of the substitutes is more than 1,R₁₄ may be the same or different;

R₉ is selected from H, halogen, NO₂, CN, C(═O)NR₁₂R₁₃, C(═S)NR₁₂R₁₃,C₁-C₈alkylaminocarbonyl, C₁-C₈alkoxycarbonyl, C₁-C₈haloalkyl orC₁-C₈alkylsulfonyl;

R₁₀ is selected from H, halogen, OH, CN, NO₂, COOH, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈halo alkoxy, C₁-C₈alkylamino,C₁-C₈halo alkylamino, C₁-C₈alkylthio, C₁-C₈halo alkylthio,C₁-C₈alkylsulfonyl, C₂-C₈dialkylamino, C₃-C₈alkenyloxy,C₃-C₈haloalkenyloxy, C₃-C₈ alkynyloxy, C₃-C₈halo alkynyloxy,C₁-C₈alkylcarbonyloxy, C₁-C₈alkylcarbonylamino, C₁-C₈alkylsulfonyloxy,C₁-C₈alkoxyC₁-C₈ alkoxy or C₁-C₈ alkoxycarbonylC₁-C₈alkoxy;

R₁₁ is selected from CN or NO₂,

R₁₂ and R₁₃ may be the same or different, respectively selected from H,C₁-C₆alkyl or C₃-C₆cycloalkyl;

R₁₄ is selected from halogen, NO₂, CN, C₁-C₆alkyl, C₁-C₆haloalkyl,C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylcarbonyl,C₁-C₆alkoxycarbonyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₃-C₆alkenyloxy,C₃-C₆haloalkenyloxy, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆alkynyloxy,C₃-C₆haloalkynyloxy, C₁-C₆haloalkylthio, C₁-C₆haloalkylcarbonyl,C₁-C₆alkylamino, C₁-C₆haloalkylamino, C₂-C₈dialkylamino,C₁-C₆alkylcarbonylamino, C₁-C₆haloalkylcarbonylamino,C₁-C₆alkylaminocarbonyl or C₁-C₆haloalkylaminocarbonyl;

Or the salts of the compounds having general formula I.

Furthermore, the preferred uses as antitumor compounds of generalformula I of this invention include two kinds of compounds:

The first kind of compound is: R₇ is Cl, R₉ and R₁₁ are CN in compoundsof general formula I, the structures are as general formula II:

Wherein:

R₁ is selected from H, C₁-C₈alkyl, C₃-C₈cycloalkyl, C₁-C₈haloalkyl,C₁-C₈alkylcarbonyl, C₁-C₈halo alkylcarbonyl, C₁-C₈alkoxycarbonyl,C₁-C₈alkylamino carbonyl, C₁-C₈alkylsulfonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈ alkoxyC₁-C₈alkylcarbonyl, C₁-C₈ alkoxycarbonylC₁-C₈alkyl,C₂-C₈alkenyl, C₂-C₈alkynyl, C₂-C₈haloalkenyl, C₂-C₈haloalkynyl, arylC₁-C₈alkyl or CO—X—CO₂R₁₂, in which X is selected from (CHR₁₂)n,CR₁₂═CR₁₃ or C₆H₄, n=1-6;

R₂ and R₆ may be the same or different, respectively selected from H,halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈halo alkyl,C₁-C₈alkoxy, C₁-C₈halo alkoxy, C₁-C₈alkylthio, C₁-C₈halo alkylthio,C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl,C₁-C₈alkoxycarbonyl, C₁-C₈ alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl, or the following groups unsubstituted orsubstituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy, arylamino,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl orheteroaryloxy, and when the number of the substitutes is more than 1,R₁₄ may be the same or different;

R₃ and R₅ may be the same or different, respectively selected from H,halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈halo alkyl, C₁-C₈alkoxy, C₁-C₈halo alkoxy, C₁-C₈alkylamino, C₁-C₈halo alkylamino,C₁-C₈alkylthio, C₁-C₈halo alkylthio, C₂-C₈alkenyl, C₂-C₈alkynyl,C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl, C₁-C₈ alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkylcarbonyloxy,C₁-C₈ alkoxycarbonyloxy, C₁-C₈alkylaminocarbonyloxy,C₁-C₈alkylsulfonyloxy, C₁-C₈ alkoxyC₁-C₈ alkoxy,C₁-C₈haloalkoxyC₁-C₈haloalkoxy, C₁-C₈ alkoxycarbonylC₁-C₈ alkoxy, or thefollowing groups unsubstituted or substituted with 1-5 R₁₄: aryl,arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl,aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the numberof the substitutes is more than 1, R₁₄ may be the same or different;

R₄ is selected from H, halogen, CN, NO₂, COOH, CO₂Na, CO₂NH₄,C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈halo alkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₂-C₈ alkenyl, C₂-C₈ alkynyl, C₁-C₈alkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈ alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈ alkoxy,C₁-C₈haloalkoxyC₁-C₈haloalkoxy, SO₂NR₁₂R₁₃, or the following groupsunsubstituted or substituted with 1-5 R₁₄: aryl, arylmethyl,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl or arylaminocarbonyl,and when the number of the substitutes is more than 1, R₁₄ may be thesame or different;

R₈ and R₁₀ may be the same or different, respectively selected from H,halogen, OH, CN, NO₂, COOH, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₁-C₈alkylamino, C₁-C₈haloalkylamino, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, C₂-C₈dialkylamino,C₃-C₈alkenyloxy, C₃-C₈haloalkenyloxy, C₃-C₈ alkynyloxy,C₃-C₈haloalkynyloxy, C₁-C₈alkylcarbonyloxy, C₁-C₈alkylcarbonylamino,C₁-C₈alkylsulfonyloxy, C₁-C₈ alkoxyC₁-C₈ alkoxy orC₁-C₈alkoxycarbonylC₁-C₈ alkoxy;

R₁₂ and R₁₃ may be the same or different, respectively selected from H,C₁-C₆alkyl or C₃-C₆cycloalkyl;

R₁₄ is selected from halogen, NO₂, CN, C₁-C₆alkyl, C₁-C₆haloalkyl,C₁-C₆alkoxy, C₁-C₆halo alkoxy, C₁-C₆alkylthio, C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₃-C₆alkenyloxy,C₃-C₆haloalkenyloxy, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆alkynyloxy,C₃-C₆haloalkynyloxy, C₁-C₆haloalkylthio, C₁-C₆haloalkylcarbonyl,C₁-C₆alkylamino, C₁-C₆halo alkylamino, C₂-C₈dialkylamino,C₁-C₆alkylcarbonylamino, C₁-C₆halo alkylcarbonylamino, C₁-C₆alkylaminocarbonyl or C₁-C₆halo alkylamino carbonyl;

Or the salts of the compounds having general formula II.

The preferred uses as antitumor compounds of general formula II of thisinvention are:

R₁ is selected from H, C₁-C₄alkyl, C₃-C₆cycloalkyl, C₁-C₄haloalkyl,C₁-C₄alkylcarbonyl, C₁-C₄halo alkylcarbonyl, C₁-C₄ alkoxycarbonyl,C₁-C₄alkylsulfonyl, C₁-C₄ alkoxyC₁-C₄alkyl,C₁-C₄alkoxyC₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonylC₁-C₄alkyl,C₂-C₄alkenyl, C₂-C₄alkynyl, C₂-C₄haloalkenyl, C₂-C₄haloalkynyl, benzyl,phenethyl or CO—X—CO₂R₁₂, in which X is selected from (CHR₁₂)n,CR₁₂═CR₁₃ or C₆H₄, n=1-3;

R₂ and R₆ may be the same or different, respectively selected from H,Cl, Br, F, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₄alkyl, C₁-C₄halo alkyl,C₁-C₄alkoxy, C₁-C₄halo alkoxy, C₁-C₄alkylthio, C₁-C₄halo alkylthio,C₂-C₄ alkenyl, C₂-C₄alkynyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl,C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkoxycarbonylC₁-C₄alkyl, or the following groups unsubstituted orsubstituted with 1-3 R₁₄: phenoxy, phenylamino, phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, andwhen the number of the substitutes is more than 1, R₁₄ may be the sameor different;

R₃ and R₅ may be the same or different, respectively selected from H,Cl, Br, F, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₄alkyl, C₁-C₄haloalkyl,C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylamino, C₁-C₄halo alkylamino,C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₂-C₄alkenyl, C₂-C₄alkynyl,C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, C₁-C₄ alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkoxycarbonylC₁-C₄alkyl, or the following groupsunsubstituted or substituted with 1-3 R₁₄: phenoxy, phenylamino,phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl orpyridyloxy, and when the number of the substitutes is more than 1, R₁₄may be the same or different;

R₄ is selected from H, Cl, Br, F, CN, NO₂, COOH, CO₂Na, CO₂NH₄,C(═O)NR₁₂R₁₃, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₂-C₄alkenyl, C₂-C₄alkynyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl,C₁-C₄ alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkoxycarbonylC₁-C₄alkyl, C₁-C₄alkoxyC₁-C₄alkoxy, SO₂NHCH₃, SO₂N(CH₃)₂,or the following groups unsubstituted or substituted with 1-3 R₁₄:phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl or phenylaminocarbonyl,and when the number of the substitutes is more than 1, R₁₄ may be thesame or different;

R₈ and R₁₀ may be the same or different, respectively selected from Cl,Br, F, OH, CN, NO₂, C₁-C₄alkyl, C₁-C₄halo alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylamino, C₁-C₄halo alkylamino, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfonyl, C₂-C₆dialkylamino, C₃-C₄ alkenyloxy,C₃-C₄haloalkenyloxy, C₃-C₄alkynyloxy, C₃-C₄haloalkynyloxy,C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy,C₁-C₄ alkoxyC₁-C₄alkoxy or C₁-C₄alkoxycarbonylC₁-C₄ alkoxy;

R₁₂ and R₁₃ may be the same or different, respectively selected from Hor C₁-C₄alkyl; R₁₄ is selected from F, Cl, Br, NO₂, CN, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄halo alkoxy, C₁-C₄alkylthio,C₁-C₄alkylcarbonyl, C₁-C₄ alkoxycarbonyl or C₁-C₄alkylaminocarbonyl;

Or the salts of the compounds having general formula II.

Furthermore, the preferred uses as antitumor compounds of generalformula II of this invention are:

R₁ is selected from H, CH₃, acetyl, methylsulfonyl, benzyl or phenethyl;

R₂ and R₆ may be the same or different, respectively selected from H, F,Cl, Br, CN, NO₂, COOH, CONH₂, CONHCH₃, CON(CH₃)₂, CONHCH(CH₃)₂,CONHC(CH₃)₃, CH₃, C₂H₅, CH(CH₃)₂, C(CH₃)₃, ClCH₂, CF₃, CH₃O, C₂H₅O,CF₃O, CF₃CH₂O, CH₃S, CH₃OCO or CH₃OCH₂;

R₃ and R₅ may be the same or different, respectively selected from H, F,Cl, Br, CN, NO₂, COOH, CONH₂, CONHCH₃, CON(CH₃)₂, CONHCH(CH₃)₂,CONHC(CH₃)₃, CH₃, C₂H₅, CH(CH₃)₂, C(CH₃)₃, ClCH₂, CF₃, CH₃O, C₂H₅O,CF₃O, CF₃CH₂O, CH₃S, CH₃OCO or CH₃OCH₂;

R₄ is selected from H, F, Cl, Br, CN, NO₂, COOH, CO₂Na, CO₂NH₄, CONH₂,CONHCH₃, CON(CH₃)₂, CONHCH(CH₃)₂, CONHC(CH₃)₃, CF₃, CF₃O, CH₃OCO,C₂H₅OCO, CH₃SO₂, SO₂NHCH₃, SO₂N(CH₃)₂, phenoxycarbonyl,phenylaminocarbonyl, 4-CH₃-phenylaminocarbonyl or4-Cl-phenylaminocarbonyl;

R₈ and R₁₀ may be the same or different, respectively selected from Cl,F, CH₃O, CF₃O, CF₃CH₂O, CH₃NH, (CH₃)₂N, (C₂H₅)₂N, CF₃CH₂NH, ClCH₂CH₂NH,CH₃S, C₂H₅S, CH₃SO₂, C₂H₅SO₂, (CH₃)₂N, CH₂═CHCH₂O, C≡CCH₂O, ClC≡CCH₂O,IC≡CCH₂O, CH₃CO₂, CH₃CONH, CH₃OCH₂CH₂O, C₂H₅OCH₂CH₂O, CH₃OC(═O)CH₂O orCH₃OC(═O)CH₂CH₂O;

Or the salts formed from the compounds of general formula II withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

Even more preferred uses as antitumor compounds of general formula II ofthis invention are:

R₁ is selected from H;

R₂ is selected from H, F, Cl, Br, CH₃, C₂H₅, NO₂ or CN;

R₃ is selected from H, F, Cl, Br, CH₃ or CF₃;

R₄ is selected from H, F, Cl, Br, CF₃, CF₃O, CH₃OCO, CN, NO₂, COOH,CO₂Na, phenylaminocarbonyl or 4-Cl-phenylaminocarbonyl;

R₅ is selected from H, Cl, Br, CH₃ or CF₃;

R₆ is selected from H, F, Cl, Br, CH₃, C₂H₅, NO₂ or CN;

R₈ is selected from Cl, CH₃O, CH₃NH, (CH₃)₂N or (C₂H₅)₂N;

R₁₀ is selected from Cl, CH₃O or CH₃NH;

Or the salts formed from the compounds of general formula II withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

The more preferred uses as antitumor compounds of general formula II ofthis invention are:

R₁, R₃ and R₅ are selected from H;

R₂ and R₆ are selected from H, Cl or Br;

R₄ is selected from H, Cl, Br, NO₂, CF₃, CF₃O or CH₃OCO;

R₈ and R₁₀ are selected from Cl;

Or the salts formed from the compounds of general formula II withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

The most preferred uses as antitumor compounds of general formula II ofthis invention are:

The following structure in the most preferred uses as antitumorcompounds of general formula II of this invention has never beenreported before (refer to compound Table 6-112):

The second kind of compound of the preferred uses as antitumor compoundsof general formula I of this invention is: R₇ is CH₃, R₁₀ is H, R₁₁ isNO₂, the structures are as general formula III:

Wherein:

R₁ is selected from H, C₁-C₈alkyl, C₃-C₈cycloalkyl, C₁-C₈haloalkyl,C₁-C₈alkylcarbonyl, C₁-C₈halo alkylcarbonyl, C₁-C₈ alkoxycarbonyl,C₁-C₈alkylamino carbonyl, C₁-C₈alkylthio, C₁-C₈halo alkylthio,C₁-C₈alkylsulfonyl, C₁-C₈ alkoxyC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl,C₁-C₈alkylaminothio, C₂-C₈dialkylaminothio or CO—X—CO₂R₁₂, in which X isselected from (CHR₁₂)n, CR₁₂═CR₁₃ or C₆H₄, n=1-6;

R₂ and R₆ may be the same or different, respectively selected from H,halogen, CN, NO₂, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₂-C₈alkenyl, C₂-C₈alkynyl, C₁-C₈alkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, or the following groups unsubstituted orsubstituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy, arylamino,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl orheteroaryloxy, and when the number of the substitutes is more than 1,R₁₄ may be the same or different;

R₃ and R₅ may be the same or different, respectively selected from H,halogen, CN, NO₂, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈halo alkyl, C₁-C₈alkoxy, C₁-C₈halo alkoxy, C₁-C₈alkylamino, C₁-C₈halo alkylamino,C₁-C₈alkylthio, C₁-C₈halo alkylthio, C₂-C₈alkenyl, C₂-C₈alkynyl,C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl, C₁-C₈ alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkylcarbonyloxy,C₁-C₈alkoxycarbonyloxy, C₁-C₈alkylaminocarbonyloxy,C₁-C₈alkylsulfonyloxy, C₁-C₈alkoxyC₁-C₈alkoxy, C₁-C₈halo alkoxyC₁-C₈haloalkoxy, C₁-C₈ alkoxycarbonylC₁-C₈ alkoxy, or the following groupsunsubstituted or substituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy,arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl,arylaminocarbonyl or heteroaryloxy, and when the number of thesubstitutes is more than 1, R₁₄ may be the same or different;

R₄ is selected from H, halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈halo alkoxy, C₂-C₈alkenyl, C₂-C₈alkynyl, C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl,C₁-C₈ alkoxyC₁-C₈alkyl, C₁-C₈ alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈alkoxy, C₁-C₈haloalkoxyC₁-C₈haloalkoxy, or the following groupsunsubstituted or substituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy,arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl,arylaminocarbonyl or heteroaryloxy, and when the number of thesubstitutes is more than 1, R₁₄ may be the same or different;

R₈ is selected from H, halogen, C₁-C₈halo alkyl, C₁-C₈ alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylamino, C₁-C₈halo alkylamino, C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, C₃-C₈ cyclo alkyl, C₂-C₈dialkylamino,C₃-C₈ alkenyloxy, C₃-C₈haloalkenyloxy, C₃-C₈alkynyloxy,C₃-C₈haloalkynyloxy, C₁-C₈alkylcarbonyloxy, C₁-C₈alkylcarbonylamino,C₁-C₈alkylsulfonyloxy, C₁-C₈ alkoxyC₁-C₈ alkoxy,C₁-C₈alkoxycarbonylC₁-C₈alkoxy, or the following groups unsubstituted orsubstituted with 1-5 R₁₄: aryloxy, arylamino, arylmethoxy,arylmethylamino, heteroaryloxy or heteroarylamino, and when the numberof the substitutes is more than 1, R₁₄ may be the same or different;

R₉ is selected from H, halogen, NO₂, CN, C(═O)NR₁₂R₁₃, C(═S)NR₁₂R₁₃,C₁-C₈alkylamino carbonyl, C₁-C₈ alkoxycarbonyl, C₁-C₈halo alkyl orC₁-C₈alkylsulfonyl;

R₁₂ and R₁₃ may be the same or different, respectively selected from Hor C₁-C₆alkyl;

R₁₄ is selected from halogen, NO₂, CN, C₁-C₆alkyl, C₁-C₆haloalkyl,C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylcarbonyl,C₁-C₆alkoxycarbonyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₃-C₆alkenyloxy,C₃-C₆haloalkenyloxy, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆alkynyloxy,C₃-C₆haloalkynyloxy, C₁-C₆haloalkylthio, C₁-C₆haloalkylcarbonyl,C₁-C₆alkylamino, C₁-C₆halo alkylamino, C₂-C₈dialkylamino,C₁-C₆alkylcarbonylamino, C₁-C₆halo alkylcarbonylamino,C₁-C₆alkylaminocarbonyl or C₁-C₆haloalkylaminocarbonyl;

Or the salts of the compounds having general formula III.

The preferred uses as antitumor compounds of general formula III of thisinvention are:

R₁ is selected from H, C₁-C₄alkyl, C₃-C₆cycloalkyl, C₁-C₄alkylcarbonyl,C₁-C₄haloalkylcarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfonyl, C₁-C₄ alkoxyC₁-C₄alkyl,C₁-C₄alkoxyC₁-C₄alkylcarbonyl, C₁-C₄ alkoxycarbonylC₁-C₄alkyl,C₁-C₄alkylaminothio, C₂-C₄dialkylaminothio or CO—X—CO₂R₁₂, in which X isselected from (CHR₁₂)n, CR₁₂═CR₁₃ or C₆H₄, n=1-3;

R₂ and R₆ may be the same or different, respectively selected from H,halogen, CN, NO₂, C(═O)NR₁₂R₁₃, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy,C₁-C₄haloalkoxy, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₄alkylsulfonyl,C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkoxycarbonylC₁-C₄alkyl, or the following groups unsubstituted orsubstituted with 1-4 R₁₄: phenoxy, phenylamino, phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, andwhen the number of the substitutes is more than 1, R₁₄ may be the sameor different;

R₃ and R₅ may be the same or different, respectively selected from H,halogen, CN, NO₂, C(═O)NR₁₂R₁₃, C₁-C₄alkyl, C₁-C₄halo alkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylamino, C₁-C₄haloalkylamino,C₁-C₄alkylthio, C₁-C₄halo alkylthio, C₂-C₆alkenyl, C₂-C₆alkynyl,C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl or C₁-C₄alkoxyC₁-C₄alkyl;

R₄ is selected from H, halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄halo alkoxy, C₂-C₆alkenyl, C₂-C₆ alkynyl,C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄ alkoxycarbonylC₁-C₄alkyl,C₁-C₄alkoxyC₁-C₄alkoxy, or the following groups unsubstituted orsubstituted with 1-4 R₁₄: phenoxy, phenylamino, phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, andwhen the number of the substitutes is more than 1, R₁₄ may be the sameor different;

R₈ is selected from H, halogen, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylamino, C₁-C₄haloalkylamino, C₁-C₄alkylthio,C₁-C₄haloalkylthio, C₁-C₄alkylsulfonyl, C₂-C₄dialkylamino,C₃-C₄alkenyloxy, C₃-C₄haloalkenyloxy, C₃-C₆alkynyloxy,C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy,C₁-C₄ alkoxyC₁-C₄alkoxy, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, or thefollowing groups unsubstituted or substituted with 1-3 R₁₄: phenoxy,phenylamino, benzyloxy, benzylamino, pyridyloxy or pyridylamino, andwhen the number of the substitutes is more than 1, R₁₄ may be the sameor different;

R₉ is selected from Cl, Br, F, NO₂, CN, C(═O)NR₁₂R₁₃, C(═S)NR₁₂R₁₃,CO₂CH₃, CF₃ or CH₃SO₂;

R₁₂ and R₁₃ may be the same or different, respectively selected from Hor C₁-C₃alkyl;

R₁₄ is selected from halogen, NO₂, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,C₁-C₃alkoxy, C₁-C₃haloalkoxy, C₁-C₃alkylthio, C₁-C₃alkylcarbonyl, C₁-C₃alkoxycarbonyl, C₁-C₃alkylamino, C₂-C₄dialkylamino,C₁-C₃alkylcarbonylamino or C₁-C₃alkylaminocarbonyl;

Or the salts of the compounds having general formula III.

Furthermore, the preferred uses as antitumor compounds of generalformula III of this invention are:

R₁ is selected from H, CH₃, C₂H₅, cyclopropyl, formyl, acetyl, COCF₃,CO₂CH₃, CO₂C₂H₅, SCCl₃, SO₂CH₃, SO₂C₂H₅, CH₂OCH₃, CH₂OC₂H₅, CH₂CH₂OCH₃,COCH₂OCH₃, CH₂COOCH₃, SNHCH₃, SN(CH₃)₂, COCH₂CO₂H, COCH₂CO₂CH₃,COCH₂CH₂CO₂H, COCH₂CH₂CO₂CH₃, COCHCH₃CO₂H, COCHCH₃CO₂CH₃, COC₆H₄CO₂H,COC₆H₄CO₂CH₃, COCH═CHCO₂H or COCH═CHCO₂CH₃;

R₂ and R₆ may be the same or different, respectively selected from H,Cl, Br, F, CN, NO₂, C(═O)NH₂, C(═O)NHCH₃, C(═O)N(CH₃)₂, CH₃, C₂H₅, CF₃,OCH₃, OC₂H₅, OCF₃, SO₂CH₃, SO₂C₂H₅, COCH₃, CO₂CH₃, CO₂C₂H₅, phenoxy,phenylamino, phenoxycarbonyl or phenylaminocarbonyl;

R₃ and R₅ may be the same or different, respectively selected from H,Cl, Br, F, CN, NO₂, C(═O)NH₂, CH₃, CF₃, OCH₃, OCF₃, NHCH₃, SCH₃, SO₂CH₃,SO₂C₂H₅, COCH₃, CO₂CH₃, CO₂C₂H₅ or CH₂OCH₃;

R₄ is selected from H, Cl, Br, F, CN, NO₂, CO₂H, C(═O)NH₂, C(═O)NHCH₃,C(═O)N(CH₃)₂, CH₃, CF₃, CF(CF₃)₂, OCF₃, OCH₂CF₃, OCF₂CHFCF₃, SO₂CH₃,SO₂C₂H₅, COCH₃, CO₂CH₃, CO₂C₂H₅, phenoxy, phenylamino, phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl, pyridyloxy or3-chloro-5-(trifluoromethyl)pyridin-2-yloxy;

R₈ is selected from H, Cl, Br, F, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy,C₁-C₃alkylamino, C₁-C₃haloalkylamino, SCH₃, SC₂H₅, N(CH₃)₂, N(C₂H₅)₂,OCH₂OCH₃, phenoxy, phenylamino, benzyloxy, benzylamino, 4-chlorophenoxy,4-chlorophenylamino, 2-chloro-4-(trifluoromethyl)phenoxy,2-chloro-4-(trifluoromethyl)phenylamino,3-chloro-5-(trifluoromethyl)pyridin-2-yloxy or3-chloro-5-(trifluoromethyl)pyridin-2-ylamino;

R₉ is NO₂;

Or the salts formed from the compounds of general formula III withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

Even more preferred uses as antitumor compounds of general formula IIIof this invention are:

R₁ is selected from H or CH₃;

R₂ and R₆ may be the same or different, respectively selected from H,Cl, Br, F, CN, NO₂, C(═O)NH₂, C(═O)NHCH₃, C(═O)N(CH₃)₂, CH₃, CF₃, CO₂CH₃or phenoxycarbonyl;

R₃ and R₅ may be the same or different, respectively selected from H,Cl, Br, F, CN, NO₂, CH₃, CF₃ or OCH₃;

R₄ is selected from H, Cl, Br, F, CN, NO₂, CO₂H, C(═O)NH₂, C(═O)NHCH₃,CH₃, CF₃, OCF₂CHFCF₃, CO₂CH₃ or3-chloro-5-(trifluoromethyl)pyridin-2-yloxy;

R₈ is selected from H, Cl, OCH₃, OCH₂CF₃, NHCH₃, SCH₃ or N(CH₃)₂;

R₉ is NO₂,

Or the salts formed from the compounds of general formula III withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

The more preferred uses as antitumor compounds of general formula III ofthis invention are:

R₁, R₃ and R₅ are selected from H;

R₂ is selected from Cl or F;

R₄ is selected from H, Cl, CN, NO₂ or CF₃;

R₆ is selected from F, Cl, CN or NO₂;

R₈ is selected from H, Cl or OCH₂CF₃;

R₉ is NO₂,

Or the salts formed from the compounds of general formula III withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

The most preferred uses as antitumor compounds of general formula III ofthis invention are:

The terms used above to definite the compounds of general formula Irepresent substitutes as follow:

The “halogen” or “halo” is fluorine, chlorine, bromine or iodine.

The “alkyl” stands for straight or branched chain alkyl, such as methyl,ethyl, propyl, isopropyl or tert-butyl.

The “cycloalkyl” is substituted or unsubstituted cyclic alkyl, such ascyclopropyl, cyclopentyl or cyclohexyl. The substitute(s) is(are)methyl, halogen, etc.

The “haloalkyl” stands for straight or branched chain alkyl, in whichhydrogen atoms can be all or partly substituted with halogen, such aschloromethyl, dichloromethyl, trichloromethyl, fluoromethyl,difluoromethyl, trifluoromethyl, etc.

The “alkoxy” refers to straight or branched chain alkyl, which is linkedto the structure by oxygen atom.

The “haloalkoxy” refers to straight or branched chain alkoxy, in whichhydrogen atoms may be all or partly substituted with halogen, such aschloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy,difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy,etc.

The “alkylthio” refers to straight or branched chain alkyl, which islinked to the structure by sulfur atom.

The “haloalkylthio” refers to straight or branched chain alkylthio, inwhich hydrogen atoms may be all or partly substituted with halogen, suchas chloromethylthio, dichloromethylthio, trichloromethylthio,fluoromethylthio, difluoromethylthio, trifluoromethylthio,chlorofluoromethylthio, etc.

The “alkylamino” refers to straight or branched chain alkyl, which islinked to the structure by nitrogen atom.

The “haloalkylamino” refers to straight or branched chain alkylamino, inwhich hydrogen atoms may be all or partly substituted with halogen.

The “alkenyl” refers to straight or branched chain alkenyl, such asethenyl, 1-propenyl, 2-propenyl and different isomer of butenyl,pentenyl and hexenyl. Alkenyl also includes polyene, such aspropa-1,2-dienyl and hexa-2,4-dienyl.

The “haloalkenyl” stands for straight or branched chain alkenyl, inwhich hydrogen atoms can be all or partly substituted with halogen.

The “alkynyl” refers to straight or branched chain alkynyl, such asethynyl, 1-propynyl, 2-propynyl and different isomer of butynyl,pentynyl and hexynyl. Alkynyl also includes groups including more thanone triple bonds, such as hexa-2,5-diynyl.

The “haloalkynyl” stands for straight or branched chain alkynyl, inwhich hydrogen atoms can be all or partly substituted with halogen.

The alkenyloxy refers to straight or branched chain alkenyl, which islinked to the structure by oxygen atom.

The alkynyloxy refers to straight or branched chain alkynyl, which islinked to the structure by oxygen atom.

The alkylsulfonyl refers to straight or branched chain alkyl, which islinked to the structure by sulfuryl(—SO₂—), such as SO₂CH₃.

The alkylcarbonyl refers to straight or branched chain alkyl, which islinked to the structure by carbonyl(—CO—), such as CH₃CO—, CH₃CH₂CO—.

The alkylcarbonyloxy: such as CH₃COO—, CH₃CH₂NHCOO—.

The alkylcarbonylamino: such as CH₃CONH—, CH₃CH₂NHCONH—.

The alkylsulfonyloxy: such as alkyl-S(O)₂—O—.

The alkoxycarbonyl: alkyl-O—CO—.

The phenylaminocarbonyl: phenyl-NH—CO—.

The aryl in aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl,arylmethylcarbonyl, aryloxycarbonyl and arylaminocarbonyl refers tophenyl or naphthyl, etc.

The “heteroaryl” stands for five member ring or six member ringcontaining one or more N, O, S hetero atoms. Such as furanyl, pyrazolyl,thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl,quinolinyl, etc.

Part of the substitutes of R₁, R₂, R₃, R₄, R₅, R₆, R₈ and R₁₀ in formulaI are separately listed in table 1, table 2, table 3, table 4 and table5, but without being restricted thereby.

TABLE 1 substitute R₁ R₁ R₁ R₁ H CO₂CH₃ CH₂C≡C—Cl CH₃ CO₂CH₂CH₃CH₂C≡CCH₃ C₂H₅ SO₂CH₂CH₃ PhCH₂ n-C₃H₇ CH₂OCH₃ PhCH₂CH₂ i-C₃H₇ CH₂CH₂OCH₃4-Cl—PhCH₂ n-C₄H₉ CH₂CH₂OCH₂CH₃ COCH₂CO₂CH₃ t-C₄H₉ COCH₂OCH₃COCH₂CH₂CO₂CH₃

COCH₂OCH₂CH₃ COCHCH₃CO₂CH₃ CH₂Cl CH₂CO₂CH₃ COCH₂COOH CF₃ CH₂CO₂CH₂CH₃COCH₂CH₂COOH CH₂CF₃ CH₂CH═CH₂ COCHCH₃COOH COCH₃ CH₂CH═CF₂ COCH═CHCOOHCOCH₂CH₃ CH₂CH₂CH═CF₂ COCH═CHCO₂CH₃ COCH₂CH₂CH₃ CONHCH₃ CH₂CH₂CF═CF₂CH₂CH═CCl₂

CONHCH₂CH₃ SO₂CH₃ CH₂C≡CH CH₂C≡C—I

TABLE 2 substitute R₂(R₆) R₂(R₆) R₂(R₆) R₂(R₆) R₂(R₆) H CH₃ OCH(CH₃)₂CH₂CO₂CH₂CH₃ F CH₂CH₃ OCF₃ Ph Cl n-C₃H₇ OCH₂CF₃ CH₂Ph Br i-C₃H₇ OCF₂CF₃OPh I n-C₄H₉ CH═CH₂ NHPh CN t-C₄H₉ CH₂CH═CH₂ COPh NO₂ CF₃ C≡CH CO₂PhCOOH CHF₂ CH₂C≡CH CO₂Ph-4-Cl CONH₂ CH₂F SO₂CH₃ CO₂Ph-2-Cl-4-CF₃ CONHCH₃CH₂Cl SO₂CH₂CH₃ CO₂Ph-2-Cl-4-NO₂ CON(CH₃)₂ CH₂Br COCH₃ CONHPh CONHCH₂CH₃CH₂CF₃ COCH₂CH₃ CONHPh-4-Cl CON(CH₂CH₃)₂ CF₂CHF₂ CO₂CH₃ CONHPh-2-ClCONH(CH₂)₂CH₃ CF₂CF₃ CO₂CH₂CH₃ CONHPh-4-NO₂ CONHCH(CH₃)₂ OCH₃ CH₂OCH₃CONHPh-2-Cl-4-CF₃ CONH(CH₂)₃CH₃ OCH₂CH₃ CH₂OCH₂CH₃ CONHPh-2-Cl-4-NO₂CONHC(CH₃)₃ O(CH₂)₂CH₃ CH₂CO₂CH₃

TABLE 3 substitute R₃(R₅) R₃(R₅) R₃(R₅) R₃(R₅) R₃(R₅) H n-C₃H₇ OCH₂CF₃CH₂Ph F i-C₃H₇ OCF₂CF₃ OPh Cl n-C₄H₉ CH═CH₂ NHPh Br t-C₄H₉ CH₂CH═CH₂COPh I CF₃ C≡CH CO₂Ph CN CHF₂ CH₂C≡CH CO₂Ph-4-Cl NO₂ CH₂F SO₂CH₃CO₂Ph-2-Cl-4-CF₃ COOH CH₂Cl SO₂CH₂CH₃ CO₂Ph-2-Cl-4-NO₂ CONH₂ CH₂Br COCH₃CONHPh CONHCH₃ CH₂CF₃ COCH₂CH₃ CONHPh-4-Cl CON(CH₃)₂ CF₂CHF₂ CO₂CH₃CONHPh-2-Cl CONHCH₂CH₃ CF₂CF₃ CO₂CH₂CH₃ CONHPh-4-NO₂ CON(CH₂CH₃)₂ OCH₃CH₂OCH₃ CONHPh-2-Cl-4-CF₃ CONH(CH₂)₂CH₃ OCH₂CH₃ CH₂OCH₂CH₃CONHPh-2-Cl-4-NO₂ CONHCH(CH₃)₂ CH₃ CH₂CH₃ O(CH₂)₂CH₃ OCH(CH₃)₂ OCF₃CH₂CO₂CH₃ CH₂CO₂CH₂CH₃ Ph

TABLE 4 substitute R₄ R₄ R₄ R₄ R₄ H CHF₂ CH₂C≡CH CONHCH(CH₃)₂ F CH₂FSO₂CH₃ CON(CH₂CH₃)₂ Cl CH₂Cl SO₂CH₂CH₃ CONHC(CH₃)₃ Br CH₂Br COCH₃ SO₂NH₂I CH₂CF₃ COCH₂CH₃ SO₂NHCH₃ CN CF₂CHF₂ CO₂CH₃ SO₂N(CH₃)₂ NO₂ CF₂CF₃CO₂CH₂CH₃ Ph COOH OCH₃ CH₂OCH₃ CH₂Ph CO₂Na OCH₂CH₃ CH₂OCH₂CH₃ COPhCO₂NH₄ O(CH₂)₂CH₃ CH₂CO₂CH₃ COCH₂Ph CH₃ OCH(CH₃)₂ CH₂CO₂CH₂CH₃ CO₂PhCH₂CH₃ OCF₃ OCH₂OCH₃ CO₂Ph-2-Cl-4-CF₃ n-C₃H₇ OCH₂CF₃ OCH₂OCH₂CH₃ CONHPhi-C₃H₇ OCF₂CF₃ CONH₂ CONHPh-4-Cl n-C₄H₉ CH═CH₂ CONHCH₃ CONHPh-4-CH₃t-C₄H₉ CH₂CH═CH₂ CON(CH₃)₂ CONHPh-2-Cl-4-NO₂ CF₃ C≡CH CONH(CH₂)₂CH₃CONHPh-2-Cl-4-CF₃

TABLE 5 substitute R₈(R₁₀) R₈(R₁₀) R₈(R₁₀) R₈(R₁₀) R₈(R₁₀) R₈(R₁₀) H CH₃OCH₃ SCH₃ OCOCH₃ F C₂H₅ OCH₂CH₃ SCH₂CH₃ OCOCH₂CH₃ Cl n-C₃H₇ OCF₃ SO₂CH₃NHCOCH₃ Br i-C₃H₇ OCH₂CF₃ SO₂CH₂CH₃ NHCOCH₂CH₃ I n-C₄H₉ NHCH₃ N(CH₃)₂OSO₂CH₃ OH t-C₄H₉ NHCH₂CH₃ N(C₂H₅)₂ OSO₂CH₂CH₃ CN CH₂Cl NH(CH₂)₂CH₃OCH₂CH═CH₂ OCH₂OCH₃ NO₂ CF₃ NHCH(CH₃)₂ OCH₂CH═CCl₂ OCH₂OCH₂CH₃ COOHCH₂CF₃ NHCH₂CF₃ OCH₂C≡CH OCH₂CO₂CH₃

The present invention is also explained by the following compoundshaving general formula II with antitumor activity in Table 6-Table 21,but without being restricted thereby.

Table 6: In formula II, R₁ is H, R₈ and R₁₀ are Cl, R₂, R₃, R₄, R₅ andR₆ (hereinafter abbreviated to R₂-R₆) are listed in following Table, thenumbers of representative compounds are Table 6-1 to Table 6-208.

TABLE 6 Num- ber R₂ R₃ R₄ R₅ R₆ 1 H H H H H 2 F H H H H 3 Cl H H H H 4Br H H H H 5 I H H H H 6 CH₃ H H H H 7 OCH₃ H H H H 8 NO₂ H H H H 9 CF₃H H H H 10 CN H H H H 11 H F H H H 12 H Cl H H H 13 H Br H H H 14 H CF₃H H H 15 H H F H H 16 H H Cl H H 17 H H Br H H 18 H H CH₃ H H 19 H Ht-C₄H₉ H H 20 H H OCH₃ H H 21 H H OCF₃ H H 22 H H NO₂ H H 23 H H CN H H24 H H CF₃ H H 25 H H CO₂CH₃ H H 26 H H SO₂CH₃ H H 27 H H CONHPh H H 28H H CONHPh-4-CH₃ H H 29 H H CONHPh-4-Cl H H 30 F F H H H 31 F H F H H 32F H H F H 33 F H H H F 34 F H Cl H H 35 F H H CF₃ H 36 H F F H H 37 H FH F H 38 Cl Cl H H H 39 Cl H Cl H H 40 Cl H H Cl H 41 Cl H H H Cl 42 ClH H H CH₃ 43 H Cl Cl H H 44 H Cl H Cl H 45 Cl H Br H H 46 Br H Cl H H 47Cl H CF₃ H H 48 Cl H H CF₃ H 49 Cl H NO₂ H H 50 Cl H H NO₂ H 51 Cl H HCN H 52 Cl H H CH₃ H 53 NO₂ H H Cl H 54 CN H H Cl H 55 CH₃ H H Cl H 56CF₃ H CN H H 57 F H CN H H 58 Cl H CN H H 59 Br H CN H H 60 NO₂ H CN H H61 t-C₄H₉ H CN H H 62 OCH₃ H CN H H 63 CO₂CH₃ H CN H H 64 SO₂CH₃ H CN HH 65 H F CN H H 66 H Cl CN H H 67 H Br CN H H 68 H NO₂ CN H H 69 H CH₃CN H H 70 H OCH₃ CN H H 71 CN H Cl H H 72 CF₃ H Cl H H 73 CO₂CH₃ H Cl HH 74 H CN Cl H H 75 H CH₃ Cl H H 76 H CF₃ Cl H H 77 CH₃ H Cl H H 78 CH₃Cl H H H 79 CH₃ H CH₃ H H 80 CH₃ H H CH₃ H 81 CH₃ H CN H H 82 CH₃ H CF₃H H 83 CH₃ H CO₂CH₃ H H 84 CH₃ H H H CO₂CH₃ 85 H CF₃ CN H H 86 H CH₃ CNH H 87 NO₂ H Cl H H 88 CN H NO₂ H H 89 F F F H H 90 F H F H F 91 F H NO₂H F 92 Cl Cl Cl H H 93 Cl H Cl H Cl 94 Cl Cl H Cl H 95 Cl H CF₃ H Cl 96Cl H OCF₃ H Cl 97 Cl H CH₃ H Cl 98 Cl H CN H Cl 99 Cl H NO₂ H Cl 100 ClH CO₂CH₃ H Cl 101 Cl H SO₂CH₃ H Cl 102 Cl H t-C₄H₉ H Cl 103 Cl H CONHPhH Cl 104 Cl H CONHPh-4-Cl H Cl 105 Cl H CO₂Na H Cl 106 Cl H COOH H Cl107 Cl H NO₂ H CH₃ 108 Cl CH₃ Cl H H 109 Cl H Cl H CN 110 Cl H NO₂ H F111 Br H OCF₃ H Br 112 Br H Br H Br 113 Br H NO₂ H Cl 114 Br H NO₂ H Br115 CH₃ H CH₃ H CH₃ 116 CH₃ H t-C₄H₉ H CH₃ 117 C₂H₅ H Cl H C₂H₅ 118 CH₃H CO₂CH₃ H Br 119 CH₃ H CO₂CH₃ H NO₂ 120 CH₃ H CO₂CH₃ H CN 121 CH₃ HCO₂CH₃ H OCH₃ 122 CH₃ H CO₂CH₃ H CF₃ 123 CH₃ H CO₂CH₃ H Cl 124 CH₃ H ClH NO₂ 125 C₂H₅ H NO₂ H F 126 C₂H₅ H NO₂ H Cl 127 C₂H₅ H NO₂ H Br 128C₂H₅ H NO₂ H NO₂ 129 C₂H₅ H NO₂ H CN 130 C₂H₅ H NO₂ H OCH₃ 131 C₂H₅ HNO₂ H CF₃ 132 C₂H₅ H NO₂ H CO₂CH₃ 133 C₂H₅ H NO₂ H SO₂CH₃ 134 C₂H₅ Cl HH C₂H₅ 135 Cl H CN H F 136 Cl H CN H Br 137 Cl H CN H NO₂ 138 Cl H CN HOCH₃ 139 Cl H CN H CO₂CH₃ 140 F H CN H Br 141 F H CN H NO₂ 142 F H CN HOCH₃ 143 F H CN H CO₂CH₃ 144 Cl H SO₂NHCH₃ H Cl 145 Cl H SO₂N(CH₃)₂ H Cl146 Cl H CO₂NH₄ H Cl 147 Cl H CONH₂ H Cl 148 Cl H CONHCH₃ H Cl 149 Cl HCON(CH₃)₂ H Cl 150 Cl H CONHCH(CH₃)₂ H Cl 151 Cl H CONHC(CH₃)₃ H Cl 152CH₃ H Cl CH₃ H 153 NO₂ H Cl H NO₂ 154 CN H Cl H NO₂ 155 CN H Cl H CH₃156 CN H Cl H CN 157 CN H Cl H CF₃ 158 CO₂CH₃ H Cl H Cl 159 CH₃ H Cl HCl 160 NO₂ H Cl H Cl 161 CF₃ H Cl H Cl 162 OCH₃ H Cl H Cl 163 NO₂ H Cl HF 164 NO₂ H Cl H Br 165 NO₂ H Cl H CF₃ 166 NO₂ H Cl H CO₂CH₃ 167 NO₂ HCl H CH₃ 168 CN H NO₂ H NO₂ 169 COOH H CN H CH₃ 170 COOH H Cl H Cl 171COOH H Cl H CH₃ 172 COOH H Br H CH₃ 173 COOH H CN H Cl 174 CO₂CH₃ H Cl HCH₃ 175 CO₂CH₃ H Br H CH₃ 176 CONHCH₃ H CN H CH₃ 177 CONHCH₃ H Cl H Cl178 CONHCH₃ H Cl H CH₃ 179 CONHCH₃ H Br H CH₃ 180 CONHCH₃ H H H H 181CONH₂ H CN H CH₃ 182 CONH₂ H Cl H Cl 183 CONH₂ H Cl H CH₃ 184 CONH₂ H BrH CH₃ 185 CONH₂ H CN H Cl 186 CON(CH₃)₂ H CN H CH₃ 187 CON(CH₃)₂ H Cl HCl 188 CON(CH₃)₂ H Cl H CH₃ 189 CON(CH₃)₂ H Br H CH₃ 190 CON(CH₃)₂ H CNH Cl 191 CONHCH(CH₃)₂ H CN H CH₃ 192 CONHCH(CH₃)₂ H Cl H Cl 193CONHCH(CH₃)₂ H Cl H CH₃ 194 CONHCH(CH₃)₂ H Br H CH₃ 195 CONHCH(CH₃)₂ HCN H Cl 196 CONHC(CH₃)₃ H CN H CH₃ 197 CONHC(CH₃)₃ H Cl H Cl 198CONHC(CH₃)₃ H Cl H CH₃ 199 CONHC(CH₃)₃ H Br H CH₃ 200 CONHC(CH₃)₃ H CN HCl 201 Cl H Br H Cl 202 Cl H SO₂NH₂ H Cl 203 Cl H SO₂NH₂ H Br 204 Br HSO₂NH₂ H Br 205 Cl CH₃ CN Cl H 206 CH₃ Cl NO₂ H NO₂ 207 NO₂ CH₃ Cl H NO₂208 CN Cl CN Cl Cl

Table 7: In formula II, R₁ is CH₃, R₈ and R₁₀ are Cl, R₂-R₆ are listedin Table 6, the number of representative compounds are Table 7-1 toTable 7-208.

Table 8: In formula II, R₁ is H, R₈ and R₁₀ are F, R₂-R₆ are listed inTable 6, the number of representative compounds are Table 8-1 to Table8-208.

Table 9: In formula II, R₁ is H, R₈ is N(C₂H₅)₂, R₁₀ is Cl, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 9-1to Table 9-208.

Table 10: In formula II, R₁ is H, R₈ is N(CH₃)₂, R₁₀ is Cl, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 10-1to Table 10-208.

Table 11: In formula II, R₁ is H, R₈ is NHCH₃, R₁₀ is Cl, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 11-1to Table 11-208.

Table 12: In formula II, R₁ is H, R₈ is OCH₃, R₁₀ is Cl, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 12-1to Table 12-208.

Table 13: In formula II, R₁ is H, R₈ is SCH₃, R₁₀ is Cl, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 13-1to Table 13-208.

Table 14: In formula II, R₁ is H, R₈ and R₁₀ are OCH₃, R₂-R₆ are listedin Table 6, the number of representative compounds are Table 14-1 toTable 14-208.

Table 15: In formula II, R₁ is H, R₈ and R₁₀ are N(CH₃)₂, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 15-1to Table 15-208.

Table 16: In formula II, R₁ is H, R₈ and R₁₀ are NHCH₃, R₂-R₆ are listedin Table 6, the number of representative compounds are Table 16-1 toTable 16-208.

Table 17: In formula II, R₁ is H, R₈ and R₁₀ are SCH₃, R₂-R₆ are listedin Table 6, the number of representative compounds are Table 17-1 toTable 17-208.

Table 18: In formula II, R₁ is H, R₈ is SO₂CH₃, R₁₀ is Cl, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 18-1to Table 18-208.

Table 19: In formula II, R₁ is H, R₈ is OCH₂CH═CH₂, R₁₀ is Cl, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 19-1to Table 19-208.

Table 20: In formula II, R₁ is H, R₈ is OCH₃, R₁₀ is F, R₂-R₆ are listedin Table 6, the number of representative compounds are Table 20-1 toTable 20-208.

Table 21: In formula II, R₁ is H, R₈ is N(CH₃)₂, R₁₀ is F, R₂-R₆ arelisted in Table 6, the number of representative compounds are Table 21-1to Table 21-208.

The present invention is also explained by the following compoundshaving general formula III with antitumor activity in Table 22-Table 30,but without being restricted thereby.

Table 22: In general formula III, R₁ is H, R₈ is Cl, R₉ is NO₂, R₂, R₃,R₄, R₅ and R₆ (hereinafter abbreviated to R₂-R₆) are listed in followingTable, the numbers of representative compounds are Table 22-1 to Table22-208.

TABLE 22 Number R₂ R₃ R₄ R₅ R₆ 1 H H H H H 2 F H H H H 3 Cl H H H H 4 BrH H H H 5 I H H H H 6 CH₃ H H H H 7 OCH₃ H H H H 8 NO₂ H H H H 9 CF₃ H HH H 10 CN H H H H 11 CO₂Ph H H H H 12 H F H H H 13 H Cl H H H 14 H Br HH H 15 H CF₃ H H H 16 H H F H H 17 H H Cl H H 18 H H Br H H 19 H H CH₃ HH 20 H H OCH₃ H H 21 H H OCF₃ H H 22 H H NO₂ H H 23 H H CN H H 24 H HCF₃ H H 25 H H CO₂CH₃ H H 26 H H SO₂CH₃ H H 27 H H CONHPh H H 28 H HCONHPh-4-CH₃ H H 29 H H CONHPh-4-Cl H H 30 F F H H H 31 F H F H H 32 F HH F H 33 F H H H F 34 F H Cl H H 35 F H H CF₃ H 36 H F F H H 37 H F H FH 38 Cl Cl H H H 39 Cl H Cl H H 40 Cl H H Cl H 41 Cl H H H Cl 42 Cl H HH CH₃ 43 H Cl Cl H H 44 H Cl H Cl H 45 Cl H Br H H 46 Br H Cl H H 47 ClH CF₃ H H 48 Cl CH₃ H H H 49 Cl H H CF₃ H 50 Cl H NO₂ H H 51 Cl H H NO₂H 52 Cl H H CN H 53 Cl H H CH₃ H 54 NO₂ H H Cl H 55 CN H H Cl H 56 CH₃ HH Cl H 57 CH₃ H H H Cl 58 CH₃ Cl H H H 59 CF₃ H CN H H 60 F H CN H H 61Cl H CN H H 62 Br H CN H H 63 NO₂ H CN H H 64 t-C₄H₉ H CN H H 65 OCH₃ HCN H H 66 CO₂CH₃ H CN H H 67 SO₂CH₃ H CN H H 68 H F CN H H 69 H Cl CN HH 70 H Br CN H H 71 H NO₂ CN H H 72 H CH₃ CN H H 73 H OCH₃ CN H H 74 CNH Cl H H 75 CF₃ H Cl H H 76 CO₂CH₃ H Cl H H 77 H CN Cl H H 78 H CH₃ Cl HH 79 H CF₃ Cl H H 80 CH₃ H Cl H H 81 CH₃ H CH₃ H H 82 CH₃ H H CH₃ H 83CH₃ H CN H H 84 CH₃ H CF₃ H H 85 CH₃ H CO₂CH₃ H H 86 H CF₃ CN H H 87 HCH₃ CN H H 88 NO₂ H Cl H H 89 NO₂ H NO₂ H H 90 CN H NO₂ H H 91 F F F H H92 F H F H F 93 F H Cl H F 94 F H F H NO₂ 95 F H NO₂ H F 96 Cl Cl Cl H H97 Cl H Cl Cl H 98 Cl H Cl H Cl 99 Cl Cl H Cl H 100 Cl H Br H Cl 101 ClH CF₃ H Cl 102 Cl H OCF₃ H Cl 103 Cl H CH₃ H Cl 104 Cl H CN H Cl 105 ClH NO₂ H Cl 106 Cl H NO₂ Cl H 107 Cl H CO₂CH₃ H Cl 108 Cl H SO₂CH₃ H Cl109 Cl H SO₂NH₂ H Cl 110 Cl H SO₂NH₂ H Br 111 Br H SO₂NH₂ H Br 112 Cl Ht-C₄H₉ H Cl 113 Cl H CONHPh H Cl 114 Cl H CONHPh-4-Cl H Cl 115 Cl HCO₂Na H Cl 116 Cl H COOH H Cl 117 Cl H NO₂ H CH₃ 118 Cl H NO₂ H NO₂ 119Cl CH₃ Cl H H 120 Cl H Cl H CN 121 Cl H Cl H NO₂ 122 Cl H NO₂ H F 123 ClH NO₂ H Br 124 Cl H OCF₂CHFCF₃ Cl H 125 H Cl

Cl H 126 Br H OCF₃ H Br 127 Br H Br H Br 128 Br H NO₂ H Cl 129 Br H NO₂H Br 130 Br H NO₂ H CN 131 CH₃ H CH₃ H CH₃ 132 CH₃ H t-C₄H₉ H CH₃ 133C₂H₅ H Cl H C₂H₅ 134 CH₃ H CO₂CH₃ H Br 135 CH₃ H CO₂CH₃ H NO₂ 136 CH₂ HCO₂CH₃ H CN 137 CH₃ H CO₂CH₃ H OCH₃ 138 CH₃ H CO₂CH₃ H CF₃ 139 CH₃ ClNO₂ H H 140 CH₃ H NO₂ H Cl 141 C₂H₅ H NO₂ H F 142 C₂H₅ H NO₂ H Cl 143C₂H₅ H NO₂ H Br 144 C₂H₅ H NO₂ H NO₂ 145 C₂H₅ H NO₂ H CN 146 C₂H₅ H NO₂H OCH₃ 147 C₂H₅ H NO₂ H CF₃ 148 C₂H₅ H NO₂ H CO₂CH₃ 149 C₂H₅ H NO₂ HSO₂CH₃ 150 Cl H CF₃ H F 151 Cl H CF₃ H Br 152 Cl H CF₃ H NO₂ 153 Cl H CNH NO₂ 154 Cl H CF₃ H OCH₃ 155 Cl H CF₃ H CO₂CH₃ 156 F H CF₃ H Br 157 F HCF₃ H NO₂ 158 F H CF₃ H OCH₃ 159 F H CF₃ H CO₂CH₃ 160 Cl H SO₂NHCH₃ H Cl161 Cl H SO₂N(CH₃)₂ H Cl 162 Cl H CO₂NH₄ H Cl 163 Cl H CONH₂ H Cl 164 ClH CONHCH₃ H Cl 165 Cl H CON(CH₃)₂ H Cl 166 Cl H CONHCH(CH₃)₂ H Cl 167 ClH CONHC(CH₃)₃ H Cl 168 CH₃ H Cl H CH₃ 169 NO₂ H Cl H NO₂ 170 NO₂ H NO₂ HNO₂ 171 NO₂ H CF₃ H NO₂ 172 NO₂ H CN CF₃ H 173 CN H Cl H NO₂ 174 CN H ClH CH₃ 175 CN H Cl H CN 176 CN H Cl H CF₃ 177 CO₂CH₃ H Cl H Cl 178 CH₃ HCl H Cl 179 NO₂ H Cl H Cl 180 NO₂ H Cl Cl H 181 CF₃ H Cl H Cl 182 OCH₃ HCl H Cl 183 NO₂ H Cl H F 184 NO₂ H Cl H Br 185 NO₂ H Cl H CF₃ 186 NO₂ HCl H CO₂CH₃ 187 NO₂ H Cl H CH₃ 188 CN H NO₂ H NO₂ 189 COOH H CN H CH₃190 COOH H Cl H Cl 191 COOH H Cl H CH₃ 192 COOH H Br H CH₃ 193 COOH H CNH Cl 194 CO₂CH₃ H Cl H CH₃ 195 CO₂CH₃ H Br H CH₃ 196 CONHCH₃ H CN H CH₃197 CONHCH₃ H Cl H Cl 198 CONHCH₃ H Cl H CH₃ 199 CONHCH₃ H Br H CH₃ 200CONHCH₃ H CN H Cl 201 CONH₂ H CN H CH₃ 202 CONH₂ H Cl H Cl 203 CONH₂ HCl H CH₃ 204 CONH₂ H Br H CH₃ 205 CONH₂ H CN H Cl 206 NO₂ Cl CF₃ H NO₂207 Cl H NO₂ Cl NO₂ 208 Cl H Cl Cl NO₂

Table 23: In formula III, R₁ and R₉ are H, R₈ is Cl, R₂-R₆ are listed inTable 22, the number of representative compounds are Table 23-1 to Table23-208.

Table 24: In formula III, R₁ is CH₃, R₈ is Cl, R₉ is NO₂, R₂-R₆ arelisted in Table 22, the number of representative compounds are Table24-1 to Table 24-208.

Table 25: In formula III, R₁ is H, R₈ is OCH₃, R₉ is NO₂, R₂-R₆ arelisted in Table 22, the number of representative compounds are Table25-1 to Table 25-208.

Table 26: In formula III, R₁ is H, R₈ is SCH₃, R₉ is NO₂, R₂-R₆ arelisted in Table 22, the number of representative compounds are Table26-1 to Table 26-208.

Table 27: In formula III, R₁ is H, R₈ is NHCH₃, R₉ is NO₂, R₂-R₆ arelisted in Table 22, the number of representative compounds are Table27-1 to Table 27-208.

Table 28: In formula III, R₁ is H, R₈ is N(CH₃)₂, R₉ is NO₂, R₂-R₆ arelisted in Table 22, the number of representative compounds are Table28-1 to Table 28-208.

Table 29: In formula III, R₁ is H, R₈ is OCH₂CF₃, R₉ is NO₂, R₂-R₆ arelisted in Table 22, the number of representative compounds are Table29-1 to Table 29-208.

Table 30: In formula III, R₁ and R₈ is H, R₉ is NO₂, R₂-R₆ are listed inTable 22, the number of representative compounds are Table 30-1 to Table30-208.

The compounds having formula I in present invention have been reportedin prior art, which are commercial available or can be preparedaccording to the following method. The reaction is as follow, whereinthe definitions of substituents are as defined above:

Wherein: X and Y are different, respectively selected from halogen atomor amino; Z is halogen atom; R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are defined respectively as mentioned above; R₁ are defined as mentionedabove, but R₁≠H.

According to the above preparation method, treatment of intermediate IVwith intermediate V at the presence of base gives compounds I-a ofgeneral formula I (R₁═H), which react with Z—R₁ to give compounds I-b ofgeneral formula I (R₁≠H).

The proper base mentioned above may be selected from potassiumhydroxide, sodium hydroxide, sodium carbonate, potassium carbonate,sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodiumethoxide, sodium hydride, potassium tert-butoxide or sodiumtert-butoxide and so on.

The reaction can be carried out in proper solvent, and the propersolvent mentioned may be selected from tetrahydrofuran, acetonitrile,toluene, xylene, benzene, DMF, N-methylpyrrolidone, DMSO, acetone orbutanone and so on.

The proper reaction temperature is from room temperature to boilingpoint of solvent, generally is 20-100° C.

The reaction time is in the range of 30 minutes to 20 hours, generallyis 1-10 hours.

Intermediates IV are commercially available, or prepared according tothe known methods, such as referring to Indian Journal of Chemistry,Section B: Organic Chemistry Including Medicinal Chemistry, 45B(4),972-975, 2006; Tetrahedron Letters, 44(21), 4085-4088, 2003; PL174903,etc.

Intermediate V can be prepared according to the known methods, such asreferring to JP2003292476, 052010160695, etc.

The nitration of compounds of general formula I, in which at least oneof R₂, R₄, R₆, R₉ or R₁₁ is H, can add one or several NO₂ groups tothese compounds of general formula I.

The halogenation of substituted diphenylamine compounds of generalformula I, in which R₂, R₄, R₆, R₇, R₉ or R₁₁ is not halogen atom, canadd one or several halogen atoms to these compounds of general formulaI.

The compounds of general formula I, in which R₈ and R₁₀ are alkylamino,alkoxy or alkylthio, can be prepared from the reaction of compounds ofgeneral formula I whose R₈ and R₁₀ are halogen atom with amine, alcoholor mercaptan (or their salts), or referring to the preparation method inJournal of Medicinal Chemistry, 1978, 21(9), 906-913.

The compounds of general formula I, in which R₈ and R₁₀ arealkylsulfonyl and alkylcarbonyloxy, can be prepared according to thepreparation method in Journal of Medicinal Chemistry, 1978, 21(9),906-913.

The salts of compounds having general formula I can be prepared from thereaction of the compounds of general formula I with corresponding acidaccording to routine method. The proper acid may be selected fromhydrochloric acid, sulfuric acid, nitric acid, carbonic acid, phosphoricacid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonicacid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citricacid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbicacid or oxalic acid; The preferred acid are selected from hydrochloricacid, sulfuric acid, phosphoric acid, trifluoroacetic acid,methylsulfonic acid or p-toluenesulfonic acid.

The present invention includes the formulations, which were made fromthe compounds having the general formula I as active ingredient, andpreparation thereof. The preparation of formulations: Dissolve thecompounds of present invention in water soluble organic solvents, theionicity of surfactant, water soluble lipid, all kinds of cyclodextrin,fatty acid, fatty acid ester, phospholipids or their combinationsolvents, and add physiological saline or 1-20% of carbohydrates.Mentioned organic solvents include polyethylene glycol (PEG), ethanol,propylene glycol or their combination solvents.

The compounds having the general formula I in present invention andtheir salt and prodrug can be used to prepare the drugs or formulationsto cure, prevent or alleviate cancer. The active ingredients arecomposed of one or more than two diphenylamine compounds having thegeneral formula I. Especially to cure or alleviate the cancer causing bycancer cells of human tissue or organ. The preferred cancers are: coloncancer, liver cancer, lymph cancer, lung cancer, esophageal cancer,breast cancer, central nervous system cancer, melanoma, ovarian cancer,cervical cancer, renal cancer, leukemia, prostatic cancer, pancreaticcancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx canceror stomach cancer.

The compounds in present invention can be used as active ingredients ofantitumor drug, which can be used alone or combined with otherantitumorantiviral drugs. The drug combination process in presentinvention, using at least one of the compounds and its activederivatives with other one or more antitumorantiviral drugs, are usedtogether to increase the overall effect. The dose and drugadministration time of combination therapy are based on the mostreasonable treatment effect in the different situations.

The formulations include the effective dose of the compounds havinggeneral formula I. The “effective dose” refers to the compound dosage,which are effective to cure cancer. The effective dose or dose can bedifferent based on the suggestions of experienced person at differentconditions. For instance, the different usage of drug based on differentcancers; the dose of drug also can be changed based on whether it shareswith other therapeutic method, such as antitumor or antiviral drugs. Thedrug can be prepared for any useable formulations. The salts ofcompounds also can be used if the alkaline or acidic compounds canformed the non-toxic acids or salts. The organic acids/salts in pharmacyinclude anion salts, which are formed with acids, such asp-toluenesulfonic acid, methylsulfonic acid, acetic acid, benzoic acid,citric acid, malic acid, tartaric acid, maleic acid, succinic acid,ascorbic acid or glycerophosphoric acid; the inorganic salts includechloride, bromide, fluoride, iodide, sulfate, nitrate, bicarbonate,carbonate or phosphate. For example, the alkaline compounds, such asamines can form salts with suitable acids; acids can form salts withalkalis or alkaline earth.

The compounds in present invention having general formula I generaleasily dissolves in organic solvent, water soluble solvent and theirmixture with water. The water soluble solvents prefer alcohol,polyethylene glycol, N-methyl-2-pyrrolidone, N,N-dimethyl acetamide,N,N-dimethyl formamide, dimethylsulfoxide, acetonitrile and theirmixture. Mentioned alcohols prefer methanol, ethanol, isopropanol,glycerol or ethylene glycol. The compounds in present invention mix withcommon drug carrier to form formulations. Dissolve the compounds ofpresent invention in water soluble organic solvents, aprotic solvent,water soluble lipid, cyclodextrin, fatty acid, phospholipids or theircombination solvents, and add physiological saline or 1-20% ofcarbohydrates, such as glucose aqueous solution. The stabilityformulations made by this way are used for animal and clinical.

The drugs were made from the active ingredients of general formula Icompounds, which can dose by oral medication or parenteral route, alsoby implantable medication pump and other methods. Where the parenteralroute refer to injection or drip technology through subcutaneousintradermal, intramuscular, intravenous, arteries, atrium, synovium,sternum, intrathecal, wound area, encephalic, etc. The formulations weremixed using conventional method by technicist, which are used for animaland clinical, including tablets, pills, capsule, granule, syrup,injection, freeze-dried powder injection, emulsion, powder, freeze-driedpowder, drop pill, milk suspension, aqueous suspension, colloid,colloidal solution, sustained-release suspensions, nanoparticle or otherformulations.

The compounds having the general formula I in present invention can beused to cure or alleviate the cancer causing by cancer cells of humantissue or organ. The cancers include but not limited to colon cancer,liver cancer, lymph cancer, lung cancer, esophageal cancer, breastcancer, central nervous system cancer, melanoma, ovarian cancer,cervical cancer, renal cancer, leukemia, prostatic cancer, pancreaticcancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx canceror stomach cancer.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is illustrated by the following examples, butwithout being restricted thereby. (All raw materials are commerciallyavailable unless otherwise specified.)

PREPARATION EXAMPLES Example 1 Preparation of Compound Table 6-1

0.35 g (3.76 mmol) of aniline and 0.30 g (7.52 mmol) of sodium hydroxidewere added into 40 mL of DMF, and 1.00 g (3.76 mmol) of2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring,then stirred for another 5 h. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water,and filtered to give white solid. The solid was washed twice by 30 mlwater and twice by 20 ml petroleum ether, 0.65 g of compound Table 6-1as white solid was obtained, m.p. 226-228° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):7.22 (d, 2H, Ph-2,6-2H, J=7.5 Hz), 7.40-7.46 (m, 3H, Ph-3,4,5-3H).

Example 2 Preparation of Compound Table 6-33

1.03 g (8 mmol) of 2,6-difluoroaniline and 0.64 g (16 mmol) of sodiumhydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring,then stirred for another 5 h. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water,and extracted with ethyl acetate, the extract was washed by water andsaturated brine, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was purified through silica column(ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, asan eluent) to give 1.65 g of compound table 6-33 as yellow solid, m.p.264-266° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):6.70 (s, 1H, NH), 7.07 (t, 2H, Ph-3,5-2H, J=8.1 Hz), 7.37 (m, 1H,Ph-4-1H).

Example 3 Preparation of Compound Table 6-39

The preparation is same to compound Table 6-1, brown black solid, m.p.209-212° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):6.95 (s, 1H, NH), 7.20 (d, 1H, Ph-6-H, J=8.1 Hz), 7.36 (dd, 1H, Ph-5-H,³J=8.7 Hz, ⁴J=2.7 Hz), 7.54 (d, 1H, Ph-3-H, J=2.4 Hz).

Example 4 Preparation of Compound Table 6-91

0.68 g (2 mmol) of compound table 6-33 was dissolved in 20 mL ofconcentrated sulfuric acid and cooled by ice-bath, the mixed acid (4mmol of nitric acid and 6 mmol of sulfuric acid) was added dropwise tothe reaction solution under stirring to keep the temperature below 20°C. Then the reaction mixture was stirred for another 5 min. After thereaction was over by Thin-Layer Chromatography monitoring, the reactionmixture was poured into ice water, extracted with ethyl acetate, theextract was washed by saturated brine, dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue waspurified through silica column (ethyl acetate/petroleum ether (boilingpoint range 60-90° C.)=1/4, as an eluent) to give 0.40 g of compoundtable 6-91 as white solid, m.p. 204-206° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):6.70 (s, 1H, NH), 7.97-8.01 (dd, 2H, Ph-3,5-2H, ³J=10.8 Hz, ⁴J=3.0 Hz).

Example 5 Preparation of Compound Table 6-93

1.57 g (8 mmol) of 2,4,6-trichloroaniline and 0.64 g (16 mmol) of sodiumhydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring,then stirred for another 5 h. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water,and extracted with ethyl acetate, the extract was washed by water andsaturated brine, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was purified through silica column(ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, asan eluent) to give 1.91 g of compound table 6-39 as light yellow solid,m.p. 182-184° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):6.86 (s, 1H, NH), 7.48 (s, 2H, Ph-3,5-2H).

Example 6 Preparation of Compound Table 6-99

0.35 g (1.3 mmol) of 2,6-dichloro-4-nitroaniline and 0.10 g (2.6 mmol)of sodium hydroxide were added into 40 mL of DMF, and 0.27 g (1.3 mmol)of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring,then stirred for another 5 h. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water,and extracted with ethyl acetate, the extract was washed by water andsaturated brine, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was purified through silica column(ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, asan eluent) to give 0.48 g of compound table 6-99 as yellow solid, m.p.250-252° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):6.93 (s, 1H, NH), 8.34 (s, 2H, Ph-3,5-2H).

Example 7 Preparation of Compound Table 6-100

10.33 g (39 mmol) of methyl 4-amino-3,5-dichlorobenzoate (preparationrefer to WO2010060379, CN101337940) and 3.12 g (78 mmol) of sodiumhydroxide were added into 60 mL of DMF, and 10.37 g (39 mmol) of2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring,then stirred for another 5 h. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water,and extracted with ethyl acetate, the extract was washed by water andsaturated brine, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was purified through silica column(ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/5, asan eluent) to give 13.65 g of compound table 6-100 as yellow solid, m.p.229-231° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):3.96 (s, 3H, CH₃), 6.92 (s, 1H, NH), 8.11 (s, 2H, Ph-2,6-2H).

Example 8 Preparation of Compound Table 6-104

(1) Preparation of Compound Table 6-106

13.31 g (31 mmol) of compound Table 6-100 was dissolved in mixedsolution of THF and water (volume ratio=1/1), and 2.45 g (61 mmol) ofsodium hydroxide was added to the reaction solution followed by heatingfor 5 h at 50° C. in oil-bath. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water,and extracted with ethyl acetate, the aqueous phase was acidized bydiluted hydrochloric acid, and filtered to give compound Table 6-106 asyellow solid, dried for the next step.

(2) Preparation of Compound Table 6-106a

5.54 g (12.72 mmol) of compound Table 6-106 was added to 100 ml ofpetroleum ether, and two drops of DMF and 2.27 g (19.08 mmol) of thionylchloride were added to the reaction solution followed by refluxing for 2h at 85° C. in oil-bath. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was concentrated underreduced pressure to obtain compound Table 6-106a.

(3) Preparation of Compound Table 6-104

0.12 g (0.91 mmol) of p-chloroaniline and 0.23 g (2.27 mmol) oftriethylamine were dissolved in anhydrous THF, then 0.40 g (0.91 mmol)of compound Table 6-106a was added dropwise to the reaction solutionfollowed by heating for 5 h at 45° C. in oil-bath. After the reactionwas over by Thin-Layer Chromatography monitoring, the reaction mixturewas poured into water, and extracted with ethyl acetate, the extract waswashed by saturated brine, dried over anhydrous magnesium sulfate andconcentrated under reduced pressure. The residue was purified throughsilica column (ethyl acetate/petroleum ether (boiling point range 60-90°C.)=1/3, as an eluent) to give 0.23 g of compound table 6-104 as whitesolid, m.p. 275-276° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):7.31-7.35 (m, 2H, 4-Cl-Ph-2,6-2H), 7.81 (d, 2H, 4-Cl-Ph-3,5-2H, J=9.0Hz), 8.13 (dd, 2H, Ph-2,6-2H, ³J=15.7 Hz, ⁴J=1.2 Hz), 10.50 (d, 1H,CONH, J=12.9 Hz).

Example 9 Preparation of Compound Table 6-112

2.63 g (8 mmol) of 2,4,6-trichloroaniline and 0.64 g (16 mmol) of sodiumhydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring,then stirred for another 5 h. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water,and extracted with ethyl acetate, the extract was washed by water andsaturated brine, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was purified through silica column(ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, asan eluent) to give 3.22 g of compound table 6-112 as brown solid, m.p.238-239° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):6.86 (s, 1H, NH), 7.48 (s, 2H, Ph-3,5-2H).

Example 10 Preparation of Compound Table 14-99

0.55 g (1.3 mmol) of compound Table 6-99 and 0.14 g (2.5 mmol) of sodiummethoxide were dissolved in 20 ml of DMSO, followed by heating for 8 hat 95° C. in oil-bath. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into water,and extracted with ethyl acetate, the extract was washed by water andsaturated brine, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was purified through silica column(ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, asan eluent) to give 0.16 g of compound table 14-99 as yellow solid, m.p.151-153° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):4.23 (t, 6H, OCH₃, J=6.6 Hz), 6.78 (br, 1H, NH), 8.31 (d, 2H, Ph-3,5-2H,J=3.9 Hz).

Example 11 Preparation of Compound Table 22-39

0.81 g (0.005 mol) of 2,4-dichloroaniline was added in portions to asuspention of 0.4 g (0.01 mol) of NaH (60%) and 20 mL of THF, themixture was stirred for 30 min after addition, 1.56 g (0.006 mol) of2,6-dichloro-3,5-dinitrotulune in 30 mL of THF was added within 30 min,then stirred for another 5 h. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was filtered. Thefiltrate was concentrated under reduced pressure, then the residue waspurified through silica column (ethyl acetate/petroleum ether (boilingpoint range 60-90° C.)=1/20, as an eluent) to give 1.37 g of compoundtable 22-39 as yellow solid, m.p. 136-137° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):2.14 (s, 3H), 6.53 (d, 1H), 7.17 (d, 1H), 7.49 (s, 1H), 8.68 (s, 1H),8.93 (s, 1H).

Example 12 Preparation of Compound Table 22-101

The preparation is same to compound Table 22-39, m.p. 143-144° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):1.98 (s, 3H), 7.66 (s, 2H), 8.70 (s, 1H), 9.10 (s, 1H).

Example 13 Preparation of Compound Table 22-105

0.83 g (0.004 mol) of 2,6-dichloro-4-nitroaniline was added in portionsto a suspention of 0.32 g (0.008 mol) of NaH (60%) and 10 mL of DMF, themixture was stirred for 30 min after addition, 1.20 g (0.0048 mol) of2,6-dichloro-3,5-dinitrotulune was added in portions within 30 min, thenstirred for another 3 h. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into 50 mL ofsaturated brine and extracted with ethyl acetate, the extract was driedover anhydrous magnesium sulfate and concentrated under reducedpressure. The residue was purified through silica column (ethylacetate/petroleum ether (boiling point range 60-90° C.)=1/10, as aneluent) to give 1.20 g of compound table 22-105 as yellow solid, m.p.157-158° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):2.02 (s, 3H), 8.29 (s, 2H), 8.65 (s, 1H), 8.95 (s, 1H).

Example 14 Preparation of Compound Table 22-120

The preparation is same to compound Table 22-39, m.p. 148-150° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):2.07 (s, 3H), 7.53 (s, 1H), 7.72 (s, 1H), 8.71 (s, 1H), 8.97 (s, 1H).

Example 15 Preparation of Compound Table 22-121

0.56 g (0.0015 mol) of compound table 22-39 was dissolved in 5 mL ofconcentrated sulfuric acid (96%, the same below) and cooled to 0° C.,0.15 g of fuming nitric acid (95%) and 3 mL of concentrated sulfuricacid was mixed evenly and added to the flask, then the reaction mixturewas stirred for another 5 min. After the reaction was over by Thin-LayerChromatography monitoring, the reaction mixture was poured into icewater, the solid precipitated was filtered, and the filter mass waswashed with water and dried to give 0.59 g of compound table 22-121 asbrown solid, m.p. 156-158° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):2.09 (s, 3H), 7.66 (s, 1H), 8.01 (s, 1H), 8.60 (s, 1H), 9.75 (s, 1H).

Example 16 Preparation of Compound Table 22-153

The preparation is same to compound Table 22-39, m.p. 204-206° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):2.23 (s, 3H), 7.87 (s, 1H), 8.38 (s, 1H), 8.51 (s, 1H), 10.00 (s, 1H).

Example 17 Preparation of Compound Table 22-206

The intermediate M prepared by the procedure of Example 13 was nitratedaccording to Example 2 to give compound Table 22-206 as reddish-brownsolid, m.p. 136-138° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):2.41 (s, 3H), 8.50 (s, 1H), 8.72 (s, 1H), 10.10 (s, 1H).

Example 18 Preparation of Compound Table 24-39

0.38 g (0.001 mol) of compound table 22-39 was added to a suspention of0.10 g (0.0025 mol) of NaH (60%) and 10 mL of DMF, the mixture wasstirred for 1 h and then added thereto 0.43 g (0.003 mol) of CH₃I, theresulting mixture was allowed to react for 5 h. After the reaction wasover by Thin-Layer Chromatography monitoring, the reaction mixture waspoured into 50 mL of saturated brine and extracted with ethyl acetate,the extract was dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was purified through silica column(ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/10, asan eluent) to give 0.15 g of compound table 22-39 as yellow solid, m.p.142-144° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):2.54 (s, 3H), 3.31 (s, 3H), 7.09 (d, 1H), 7.25 (d, 2H), 8.04 (s, 1H).

Example 19 Preparation of Compound Table 27-105

0.42 g of compound table 22-105 (0.001 mol) was added to a microwavevial and dissolved with 2.5 mL of DMSO, 1 mL of methylamine aqueoussolution (25%) was added, the vial was lidded and put into the microwavereactor, then the reaction was carried out at 150° C. for 40 min. Thereaction mixture was poured into 50 mL of saturated brine and extractedwith ethyl acetate, the extract was dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue waspurified through silica column (ethyl acetate/petroleum ether (boilingpoint range 60-90° C.)=120, as an eluent) to give 0.25 g of compoundtable 27-105 as yellow solid, m.p. 218-219° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):1.70 (s, 3H), 3.09 (d, 3H), 8.25 (d, 1H), 8.31 (s, 2H), 9.12 (s, 1H),9.58 (s, 1H).

Example 20 Preparation of Compound Table 29-105

0.42 g (1 mmol) of compound Table 22-105 and 2 mmol of sodium2,2,2-trifluoroethanolate (made from trifluoroethanol and sodium) weredissolved in 3 ml of DMSO, heating to 150° C. for 10 min in microwavesynthesizer (Biotage). Then the reaction mixture was poured intosaturated brine, and extracted with ethyl acetate, the extract waswashed by water and saturated brine, dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue waspurified through silica column (ethyl acetate/petroleum ether (boilingpoint range 60-90° C.)=120, as an eluent) to give 0.21 g of compoundtable 29-105 as yellow solid, m.p. 126-128° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):1.83 (s, 3H), 4.42(q, 2H), 8.30 (s, 2H), 8.85 (s, 1H), 9.20 (s, 1H).

Example 21 Preparation of Compound Table 30-105

0.83 g (0.004 mol) of 2,6-dichloro-4-nitroaniline was added in portionsto a suspention of 0.32 g (0.008 mol) of NaH (60%) and 10 mL of DMF, themixture was stirred for 30 min after addition, 1.04 g (0.0048 mol) of2-chloro-1-methyl-3,5-dinitrobenzene was added in portions within 30min, then stirred for another 3 h. After the reaction was over byThin-Layer Chromatography monitoring, the reaction mixture was pouredinto 50 mL of saturated brine and extracted with ethyl acetate, theextract was dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was purified through silica column(ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/10, asan eluent) to give 0.96 g of compound Table 30-105 as yellow solid, m.p.146-148° C.

¹H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC₃) δ(ppm):1.96 (s, 3H), 8.26 (d, 1H), 8.29 (s, 2H), 8.95 (d, 1H), 9.00 (s, 1H).

Other compounds of the present invention were prepared according to theabove examples.

Physical properties and ¹HNMR spectrum (¹HNMR, 300 MHz, internalstandard: TMS, ppm) of some compounds of this invention are as follows:

Table Compound Mp. (° C.) and ¹HNMR (300 MHz, internal standard: TMS,solvent No. No. CDCl₃) 6 3 m.p. 208-210° C. δ (CDCl₃): 7.03 (s, 1H, NH),7.27-7.38 (m, 3H, Ph-3,5,6-3H), 7.49-7.55 (m, 1H, Ph-4-H). 6 6 m.p.212-214° C. δ (CDCl₃): 2.29 (s, 3H, CH₃), 7.00 (s, 1H, NH), 7.15 (d, H,Ph-6-H, J = 7.5 Hz), 7.28-7.34 (m, 3H, Ph-3,4,5-3H). 6 10 m.p. 258-260°C. δ (CDCl₃): 7.12 (s, 1H, NH), 7.24 (d, 1H, Ph-6-H, J = 7.5 Hz), 7.47(t, 1H, Ph-4-H, J = 7.2 Hz), 7.68 (t, 1H, Ph-5-H, J = 7.5 Hz), 7.78 (d,1H, Ph-3-H, J = 7.8 Hz). 6 14 m.p. 236-238° C. δ (CDCl₃): 7.12 (s, 1H,NH), 7.28-7.40 (m, 1H, Ph-6-H), 7.41-7.52 (m, 2H, Ph-2,4-2H), 7.54-7.62(m, 1H, Ph-5-H). 6 19 m.p. 144-146° C. δ (CDCl₃): 1.30 (s, 9H, t-C₄H₉),6.65 (m, 2H, Ph-2,6-2H), 7.16 (s, 1H, NH), 7.18 (m, 2H, Ph-3,5-2H). 6 21m.p. 204-206° C. δ (CDCl₃): 7.09 (s, 1H, NH), 7.22-7.32 (m, 4H,Ph-2,3,5,6-4H). 6 23 m.p. 259-261° C. δ (CDCl₃): 7.00 (s, 1H, NH), 7.17(d, 2H, Ph-2,6-2H, J = 8.7 Hz), 7.42 (d, 2H, Ph-3,5-2H, J = 9.0 Hz). 625 m.p. 246-248° C. δ (CDCl₃): 2.29 (s, 3H, COOCH₃), 7.08 (s, 1H, NH),7.17 (d, 2H, Ph-3,5-2H, J = 8.7 Hz), 8.10 (d, 2H, Ph-2,6-2H, J = 8.7Hz). 6 31 m.p. 206-208° C. δ (CDCl₃): 6.88 (s, 1H, NH), 6.99 (t, 2H,Ph-5,6-2H, J = 8.1 Hz), 7.32 (d, 1H, Ph-3-H, J = 2.4 Hz). 6 35 m.p.209-212° C. 6.93 (s, 1H, NH), 7.34 (t, 1H, Ph-3-H, J = 9.0 Hz), 7.52 (d,1H, Ph-4-H, J = 7.2 Hz), 7.58-7.65 (m, 1H, Ph-3-H). 6 38 m.p. 218-220°C. δ (CDCl₃): 7.03 (s, 1H, NH), 7.13 (dd, 1H, Ph-6-H, ³J = 8.1 Hz, ⁴J =0.9 Hz), 7.28 (t, 1H, Ph-5-H, J = 8.1 Hz), 7.47 (dd, 1H, Ph-4-H, ³J =8.1 Hz, ⁴J = 0.9 Hz). 6 41 m.p. 235-237° C. δ (CDCl₃): 6.61 (s, 1H, NH),7.36 (t, 1H, Ph-4-H, J = 7.2 Hz), 7.45 (d, 2H, Ph-3,5-2H, J = 7.2 Hz). 642 m.p. 240-242° C. δ (CDCl₃): 2.32 (s, 3H, Ph—CH₃), 6.93 (s, 1H, NH),7.22-7.35 (m, 3H, Ph-3,4,5-H). 6 44 m.p. 238-242° C. δ (CDCl₃): 6.95 (s,1H, NH), 7.05 (d, 2H, Ph-2,6-2H, J = 1.8 Hz), 7.32 (d, 1H, Ph-4-H, J =1.5 Hz). 6 47 m.p. 166-168° C. δ (CDCl₃): 7.00 (s, 1H, NH), 7.20 (d, 1H,Ph-6-H, J = 8.4 Hz), 7.57 (dd, 1H, Ph-5-H, ³J = 8.4 Hz, ⁴J = 1.5 Hz),7.78 (s, 1H, Ph-3-H). 6 48 m.p. 197-199° C. δ (CDCl₃): 7.02 (s, 1H, NH),7.45 (s, 1H, Ph-6-H), 7.55 (d, 1H, Ph-4-H, J = 8.4 Hz), 7.65 (d, 1H,Ph-3-H, J = 8.4 Hz). 6 49 m.p. 220-222° C. 7.04 (d, 1H, Ph-6-H, J = 8.7Hz), 7.07 (s, 1H, NH), 8.20 (dd, 1H, Ph-5-H, ³J = 9.0 Hz, ⁴J = 2.7 Hz),8.42 (d, 1H, Ph-3-H, J = 2.7 Hz). 6 77 m.p. 200-202° C. δ (CDCl₃): 2.27(s, 3H, Ph-2-CH₃), 6.86 (s, 1H, NH), 7.07 (d, 1H, Ph-6-H, J = 8.4 Hz),7.23 (dd, 1H, Ph-5-H, ³J = 8.4 Hz, ⁴J = 2.1 Hz), 7.33 (s, 1H, Ph-3-H). 678 m.p. 140-142° C. δ (CDCl₃): 2.35 (s, 3H, CH₃), 6.99 (s, 1H, NH), 7.08(d, 1H, Ph-6-H, J = 8.1 Hz), 7.19-7.25 (m, 1H, Ph-5-H), 7.46 (d, 1H,Ph-4-H, J = 8.7 Hz). 6 80 m.p. 198-200° C. δ (CDCl₃): 2.23 (s, 3H, CH₃),2.34 (s, 3H, CH₃), 6.95 (s, 1H, NH), 6.95 (s, 1H, Ph-6-H), 7.13-7.22 (m,2H, Ph-3,4-2H). 6 83 m.p. 204-205° C. δ (CDCl₃): 2.36 (s, 3H, COOCH₃),3.92 (s, 3H, Ph-3-CH₃), 6.85 (s, 1H, NH), 7.12 (d, 1H, Ph-5-1H, J = 8.4Hz), 7.92 (d, 1H, Ph-6-1H, J = 8.4 Hz), 8.02 (s, 1H, Ph-2-1H). 6 84 m.p.216-218° C. δ (CDCl₃): 2.16 (s, 3H, CH₃), 3.89 (s, 3H, COOCH₃), 7.39 (t,1H, Ph-4-H, J = 7.8 Hz), 7.51 (d, 1H, Ph-5-H, J = 7.8 Hz), 7.93 (d, 1H,Ph-3-H, J = 7.8 Hz). 6 85 m.p. 242-243° C. δ (CDCl₃): 7.07 (s, 1H, NH),7.25 (d, 1H, Ph-6-H, J = 2.1 Hz), 7.42 (d, 1H, Ph-2-H, J = 2.4 Hz), 7.83(d, 1H, Ph-5-H, J = 8.4 Hz). 6 87 m.p. 232-234° C. δ (CDCl₃): 6.94 (d,1H, Ph-6-H, J = 9.3 Hz), 7.58 (dd, 1H, Ph-5-H, ³J = 9.0 Hz, ⁴J = 2.7Hz), 8.26 (d, 1H, Ph-3-H, J = 2.7 Hz), 9.36 (s, 1H, NH). 6 88 m.p.236-238° C. δ (DMSO): 7.02 (dd, 1H, Ph-6-H, ³J = 9.6 Hz, ⁴J = 2.7 Hz),8.32 (dd, 1H, Ph-5-H, ³J = 9.3 Hz, ⁴J = 2.7 Hz), 8.63 (d, 1H, Ph-3-H, J= 2.7 Hz). 6 95 m.p. 201-203° C. δ (CDCl₃): 6.91 (s, 1H, NH), 7.72 (s,2H, Ph-3,5-2H). 6 98 m.p. 259-261° C. δ (CDCl₃): 6.91 (s, 1H, NH), 7.74(s, 2H, Ph-3,5-2H). 6 103 m.p. 267-269° C. δ (CDCl₃): 7.28-7.30 (m, 1H,NHPh-4-H), 7.40 t, 2H, NHPh-3,5-2H, J = 6.9 Hz), δ = 7.62 (d, 2H,NHPh-2,6-2H, J = 7.8 Hz), δ = 7.89-7.95 (m, 2H, NHCOPh-2,6-2H). 6 107m.p. 232-234° C. δ (CDCl₃): 2.43 (s, 3H, Ph—CH₃), 6.86 (s, 1H, NH), 8.14(s, 1H, Ph-5-1H), 8.26 (s, 1H, Ph-3-1H). 6 108 m.p. 196-198° C. δ(CDCl₃): 2.55 (s, 3H, CH₃), 6.99 (s, 1H, NH), 7.04 (d, 1H, Ph-6-H, J =8.4 Hz), 7.36 (d, 1H, Ph-5-H, J = 8.4 Hz). 6 109 m.p. 194-196° C. δ(CDCl₃): 6.96 (s, 1H, NH), 7.67 (d, 1H, Ph-5-H, J = 2.1 Hz), 7.77 (d,1H, Ph-3-H, J = 2.4 Hz). 6 110 m.p. 197-199° C. 6.86 (s, 1H, NH), 8.05(dd, 1H, Ph-5-H, ³J = 9.9 Hz, ⁴J = 2.7 Hz), 8.28 (d, 1H, Ph-3-H, J = 2.4Hz). 6 113 m.p. 248-250° C. δ (CDCl₃): 6.95 (s, 1H, NH), 8.37 (d, 1H,Ph-3-H, J = 2.7 Hz), 8.49 (d, 1H, Ph-5-H, J = 2.4 Hz). 6 114 m.p.247-249° C. δ (CDCl₃): 6.96 (s, 1H, NH), 8.51 (s, 2H, Ph-3,5-2H). 6 134m.p. 176-178° C. δ (CDCl₃): 1.15-1.27 (m, 6H, CH₃), 2.49 (q, 4H, CH₂, J= 7.5 Hz), 6.98 (s, 1H, NH), 7.14 (d, 1H, Ph-5-H, J = 8.4 Hz), 7.47 (d,1H, Ph-3-H, J = 8.4 Hz). 6 152 m.p. 222-223° C. δ (CDCl₃): 2.22 (s, 3H,CH₃), 2.34 (s, 3H, CH₃), 6.88 (s, 1H, NH), 7.00 (s, 1H, Ph-6-H), 7.30(s, 1H, Ph-3-H). 6 176 m.p. 260-262° C. δ (CDCl₃): 2.06 (s, 3H, CH₃),2.98 (d, 3H, NHCH₃, J = 4.8 Hz), 6.38 (s, 1H, CONH), 7.67 (s, 2H,Ph-3,5-2H), 9.38 (s, 1H, NH). 6 178 m.p. 240-242° C. δ (CDCl₃): 2.08 (s,3H, CH₃), 2.93 (d, 3H, NCH₃, J = 5.1 Hz), 6.22 (s, 1H, CONH), 7.35-7.38(m, 2H, Ph-3,5-2H), 8.59 (s, 1H, NH). 6 180 m.p. 180-182° C. δ (CDCl₃):2.69 (s, 3H, CH₃), 7.12 (s, 1H, NH), 7.24-7.68 (m, 4H, Ph). 6 206 m.p.156-158° C. δ (CDCl₃): 2.51 (s, 3H, CH₃), 8.67 (s, 1H, Ph), 8.89 (s, 1H,NH). 9 8 Yellow oil. δ (CDCl₃): 1.13-1.21 (m, 6H, CH₃), 3.46 (q, 4H,CH₂, J = 7.2 Hz), 6.90 (s, 1H, NH), 7.13 (t, 2H, Ph-2,6-2H, J = 7.5 Hz),7.31 (d, 1H, Ph-4-H, J = 7.5 Hz), 7.42 (t, 2H, Ph-3,5-2H, J = 7.2 Hz).10 99 m.p. 127-129° C. δ (CDCl₃): 3.22 (s, 6H, CH₃), 6.85 (s, 1H, NH),8.32 (s, 2H, Ph-3,5-2H). 12 99 m.p. 198-200° C. δ (CDCl₃): 4.25 (s, 3H,CH₃), 6.87 (s, 1H, NH), 8.32 (s, 2H, Ph-3,5-2H). 14 4 m.p. 142-144° C. δ(CDCl₃): 4.14 (s, 3H, OCH₃), 4.17 (t, 3H, OCH₃, J = 4.2 Hz), 6.91 (s,1H, Ph—NH—Ph), 7.18 (d, 2H, Ph-2,6-2H, J = 7.8 Hz), 7.32 (t, 1H, Ph-4-H,J = 7.2 Hz), 7.42 (t, 2H, Ph-3,5-2H, J = 7.5 Hz). 16 2 m.p. 176-178° C.δ (CDCl₃): 3.26 (d, 3H, NCH₃, J = 8.7 Hz), 3.37 (d, 3H, NCH₃ J = 8.1Hz), 5.04 (br, 1H, Ph—NH—C), 5.26 (br, 1H, Ph—NH—C), 6.35 (s, 1H,Ph—NH—Ph), 7.04 (d, 2H, Ph-2,6-2H, J = 8.1 Hz), 7.14 (t, 1H, Ph-4-H, J =7.2 Hz), 7.35 (t, 2H, Ph-3,5-2H, J = 7.5 Hz). 22 11 m.p. 158-160° C. δ(CDCl₃): 2.10 (s, 3H), 6.83 (d, 4H), 7.12 (m, 2H), 7.34 (m, 4H), 8.56(s, 1H). 22 22 m.p. 172-174° C. δ (DMSO): 2.34 (s, 3H), 6.83 (d, 2H),8.06 (d, 2H), 8.64 (s, 1H), 9.49 (s, 1H). 22 23 m.p. 184-186° C. δ(CDCl₃): 2.22 (s, 3H), 6.87 (d, 2H), 7.62 (d, 2H), 8.66 (s, 1H), 8.93(s, 1H). 22 24 m.p. 91-94° C. δ (CDCl₃): 2.14 (s, 3H), 6.91 (d, 2H),7.21 (d, 2H), 8.71 (s, 1H), 9.20 (s, 1H). 22 31 m.p. 136-138° C. δ(CDCl₃): 2.12 (s, 3H), 7.21 (m, 2H), 7.26 (m, 1H), 8.72 (s, 1H), 9.00(s, 1H). 22 47 m.p. 106-108° C. δ (CDCl₃): 2.22 (s, 3H), 6.55 (d, 1H),7.43 (d, 1H), 7.75 (s, 1H), 8.65 (s, 1H), 8.87 (s, 1H). 22 48 m.p.110-112° C. δ (CDCl₃): 2.03 (s, 3H), 2.50 (s, 3H), 6.50 (d, 1H), 7.05(t, 1H), 7.24 (d, 1H), 8.73 (s, 1H), 9.06 (s, 1H). 22 50 m.p. 191-193°C. δ (CDCl₃): 2.29 (s, 3H), 6.48 (d, 1H), 8.06 (d, 1H), 8.41 (s, 1H),8.62 (s, 1H), 8.79 (s, 1H). 22 56 m.p. 146-148° C. δ (CDCl₃): 1.86 (s,3H), 2.40 (s, 3H), 7.18 (m, 2H), 7.28 (m, 1H), 8.80 (s, 1H), 9.52 (s,1H). 22 58 m.p. 133-135° C. δ (CDCl₃): 2.03 (s, 3H), 2.50 (s, 3H), 6.53(d, 1H), 7.06 (t, 1H), 7.21 (d, 1H), 8.74 (s, 1H), 9.08 (s, 1H). 22 61m.p. 206-208° C. δ (CDCl₃): 2.25 (s, 3H), 6.48 (d, 1H), 7.47 (d, 1H),7.77 (s, 1H), 8.62 (s, 1H), 8.80 (s, 1H). 22 63 m.p. 259-261° C. δ(CDCl₃): 2.38 (s, 3H), 6.54 (d, 1H), 7.70 (d, 1H), 8.50 (s, 1H), 8.62(s, 1H), 10.51 (s, 1H). 22 80 m.p. 121-123° C. δ (CDCl₃): 2.02 (s, 3H),2.40 (s, 3H), 6.53 (d, 1H), 7.10 (d, 1H), 7.27 (s, 1H), 8.74 (s, 1H),9.03 (s, 1H). 22 86 oil. δ (DMSO): 2.33 (s, 3H), 6.92 (d, 1H), 7.26 (s,1H), 7.78 (d, 1H), 8.63 (s, 1H), 9.54 (s, 1H). 22 88 m.p. 204-205° C. δ(CDCl₃): 2.31 (s, 3H), 6.48 (d, 1H), 7.43 (d, 1H), 8.26 (s, 1H), 8.54(s, 1H), 10.36 (s, 1H). 22 89 m.p. 185-186° C. δ (CDCl₃): 2.41 (s, 3H),6.56 (d, 1H), 8.31 (d, 1H), 8.52 (s, 1H), 9.23 (s, 1H), 10.59 (s, 1H).22 93 m.p. 148-150° C. δ (CDCl₃): 2.12 (s, 3H), 7.04 (d, 2H), 8.70 (s,1H), 8.87 (s, 1H). 22 94 m.p. 154-156° C. δ (CDCl₃): 2.21 (s, 3H), 7.20(m, 1H), 7.80 (m, 1H), 8.59 (s, 1H), 9.94 (s, 1H). 22 95 m.p. 140-142°C. δ (CDCl₃): 2.17 (s, 3H), 7.19 (d, 2H), 8.71 (s, 1H), 8.94 (s, 1H). 2297 m.p. 142-143° C. δ (CDCl₃): 2.20 (s, 3H), 6.59 (s, 1H), 7.58 (s, 1H),8.67 (s, 1H), 8.80 (s, 1H). 22 98 m.p. 160-162° C. δ (CDCl₃): 1.95 (s,3H), 7.41 (s, 2H), 8.72 (s, 1H), 9.19 (s, 1H). 22 104 m.p. 180-182° C. δ(CDCl₃): 1.99 (s, 3H), 7.69 (s, 2H), 8.67 (s, 1H), 9.00 (s, 1H). 22 106m.p. 169-171° C. δ (CDCl₃): 2.32 (s, 3H), 6.42 (s, 1H), 8.20 (s, 1H),8.60 (s, 1H), 8.62 (s, 1H). 22 107 m.p. 132-134° C. δ (CDCl₃): 1.95 (s,3H), 3.96 (s, 3H), 8.05 (s, 2H), 8.70 (s, 1H), 9.13 (s, 1H). 22 116 m.p.216-219° C. δ (CDCl₃): 2.30 (s, 3H), 7.88 (s, 2H), 8.48 (s, 1H), 8.85(s, 1H). 22 118 m.p. 169-171° C. δ (CDCl₃): 2.26 (s, 3H), 8.50 (d, 2H),8.99 (s, 1H), 10.14 (s, 1H). 22 119 m.p. 160-161° C. δ (CDCl₃): 2.13 (s,3H), 2.54 (s, 3H), 6.40 (d, 1H), 7.19 (d, 1H), 8.68 (s, 1H), 8.96 (s,1H). 22 122 m.p. 135-137° C. δ (CDCl₃): 2.16 (s, 3H), 7.95 (dd, 1H),8.26 (t, 1H), 8.63 (s, 1H), 8.82 (s, 1H). 22 123 m.p. 151-153° C. δ(CDCl₃): 1.99 (s, 3H), 8.31 (d, 1H), 8.47 (d, 1H), 8.66 (s, 1H), 9.00(s, 1H). 22 124 m.p. 96-97° C. δ (CDCl₃): 2.21 (s, 3H), 5.08 (m, 1H),6.59 (s, 1H), 7.49 (s, 1H), 8.66 (s, 1H), 8.78 (s, 1H). 22 125 m.p.192-194° C. δ (CDCl₃): 2.20 (s, 3H), 7.05 (s, 2H), 8.04 (s, 1H), 8.22(s, 1H), 9.07 (s, 1H), 9.43 (s, 1H). 22 126 m.p. 125-127° C. δ (CDCl₃):1.94 (s, 3H), 7.53 (s, 2H), 8.75 (s, 1H), 9.29 (s, 1H). 22 129 m.p.151-154° C. δ (CDCl₃): 1.97 (s, 3H), 8.49 (s, 2H), 8.68 (s, 1H), 9.03(s, 1H). 22 130 m.p. 172-175° C. δ (DMSO): 2.32 (s, 3H), 8.49 (s, 1H),8.68 (s, 2H), 9.50 (s, 1H). 22 133 m.p. 131-132° C. δ (CDCl₃): 2.10 (s,3H), 6.99 (t, 2H), 7.17 (m, 1H), 8.72 (s, 1H), 8.98 (s, 1H). 22 139 m.p.158-161° C. δ (CDCl₃): 2.16 (s, 3H), 2.61 (s, 3H), 6.47 (d, 1H), 7.67(d, 1H), 8.69 (s, 1H), 8.85 (s, 1H). 22 140 m.p. 137-139° C. δ (CDCl₃):1.91 (s, 3H), 2.31 (s, 3H), 8.10 (s, 1H), 8.21 (s, 1H), 8.73 (s, 1H),9.20 (s, 1H). 22 152 m.p. 160-162° C. δ (CDCl₃): 2.18 (s, 3H), 7.88 (d,1H), 8.32 (d, 1H), 8.55 (s, 1H), 9.97 (s, 1H). 22 163 m.p. 241-243° C. δ(CDCl₃): 1.97 (s, 3H), 7.83 (s, 2H), 8.69 (s, 1H), 9.11 (s, 1H). 22 164δ (CDCl₃): 1.94 (s, 3H), 3.03 (d, 3H), 7.78 (s, 2H), 8.70 (s, 1H), 9.14(s, 1H). 22 169 m.p. 187-190° C. δ (CDCl₃): 2.18 (s, 3H), 8.23 (s, 2H),8.57 (s, 1H), 10.39 (s, 1H). 22 170 oil. δ (CDCl₃): 2.27 (s, 3H), 8.52(s, 1H), 9.09 (s, 2H), 10.93 (s, 1H). 22 171 m.p. 93-95° C. δ (CDCl₃):2.19 (s, 3H), 8.14 (s, 2H), 8.56 (s, 1H), 10.42 (s, 1H). 22 172 m.p.204-206° C. δ (DMSO): 2.32 (s, 3H), 7.03 (s, 1H), 8.73 (s, 1H), 8.86 (s,1H), 10.40 (s, 1H). 22 180 m.p. 127-129° C. δ (CDCl₃): 2.36 (s, 3H),6.55 (s, 1H), 8.40 (s, 1H), 8.54 (s, 1H), 10.31 (s, 1H). 22 207 m.p.159-162° C. δ (CDCl₃): 2.16 (s, 3H), 8.23 (s, 1H), 8.63 (s, 1H), 8.91(s, 1H). 22 208 m.p. 133-135° C. δ (CDCl₃): 2.07 (s, 3H), 7.70 (s, 1H),8.69 (s, 1H), 9.22 (s, 1H). 23 22 m.p. 136-138° C. δ (CDCl₃): 2.22 (s,3H), 6.70 (d, 2H), 7.41 (d, 1H), 8.00 (d, 1H), 8.16 (d, 2H), 8.22 (s,1H). 23 23 m.p. 146-148° C. δ (CDCl₃): 2.19 (s, 3H), 6.70 (d, 2H), 7.36(d, 1H), 7.53 (d, 2H), 7.96 (d, 1H), 8.20 (s, 1H). 23 24 m.p. 72-74° C.δ (CDCl₃): 2.12 (s, 3H), 6.75 (d, 2H), 7.12 (d, 2H), 7.25 (d, 1H), 7.98(d, 1H), 8.46 (s, 1H). 23 63 m.p. 158-160° C. δ (CDCl₃): 2.30 (s, 3H),6.47 (d, 1H), 7.59 (m, 2H), 7.94 (d, 1H), 8.60 (s, 1H), 10.21 (s, 1H).23 77 m.p. 136-138° C. δ (CDCl₃): 2.22 (s, 3H), 6.75 (d, 1H), 7.03(s,1H), 7.45 (d, 1H), 7.67 (d, 1H), 7.99 (d, 1H), 8.16 (s, 1H). 23 80 oil.δ (CDCl₃): 2.02 (s, 3H), 2.38 (s, 3H), 6.34 (d, 1H), 7.00 (d, 1H), 7.18(m, 2H), 7.98 (d, 1H), 8.30 (s, 1H). 23 97 m.p. 112-114° C. δ (CDCl₃):2.18 (s, 3H), 6.38 (s, 1H), 7.38 (d, 1H), 7.50 (s, 1H), 7.97 (d, 1H),8.11 (s, 1H). 23 101 oil. δ (CDCl₃): 1.92 (s, 3H), 7.22 (d, 1H), 7.58(s, 2H), 7.93 (d, 1H), 8.39 (s, 1H). 24 47 m.p. 138-140° C. δ (CDCl₃):2.58 (s, 3H), 3.37 (s, 3H), 7.23 (d, 1H), 7.48 (s, 1H), 7.57 (d, 1H),8.08 (s, 1H). 24 170 m.p. 140-142° C. δ (CDCl₃): 2.58 (s, 3H), 3.30 (s,3H), 8.38 (s, 1H), 8.57 (s, 2H). 25 105 m.p. 134-136° C. δ (CDCl₃): 1.79(s, 3H), 3.96 (s, 3H), 8.29 (s, 2H), 8.74 (s, 1H), 9.18 (s, 1H). 26 105m.p. 132-134° C. δ (CDCl₃): 2.11 (s, 3H), 2.39 (s, 3H), 8.29 (s, 2H),8.47 (s, 1H), 8.95 (s, 1H). 27 164 m.p. 216-218° C. δ (CDCl₃): 1.56 (s,3H), 3.04 (m, 6H), 7.80 (s, 2H), 8.18 (s, 1H), 9.13 (s, 1H), 9.58 (s,1H). 28 105 m.p. 178-180° C. δ (CDCl₃): 1.71 (s, 3H), 2.86 (s, 6H), 8.29(s, 2H), 8.66 (s, 1H), 9.45 (s, 1H). 30 101 m.p. 155-157° C. δ (CDCl₃):1.90 (s, 3H), 7.66 (s, 2H), 8.21 (s, 1H), 8.98 (s, 1H), 9.19 (s, 1H). 30104 m.p. 183-185° C. δ (CDCl₃): 1.93 (s, 3H), 7.68 (s, 2H), 8.23 (d,1H), 8.94 (d, 1H), 9.03 (s, 1H). 30 120 m.p. 175-177° C. δ (CDCl₃): 2.00(s, 3H), 7.54 (d, 1H), 7.71 (d, 1H), 8.28 (d, 1H), 8.96 (d, 1H), 9.02(s, 1H). 30 122 m.p. 108-110° C. δ (CDCl₃): 2.11 (s, 3H), 7.95 (dd, 1H),8.26 (d, 1H), 8.31 (d, 1H), 8.79 (s, 1H), 8.92 (d, 1H).

Cell Viability Assay Example 22 In Vitro Cell Inhibition Assay (MTTMethod)

The human cancer cell lines used for this assay were lung cancer A549and leukemia HL-60.

The concentrations of compounds used for this assay were 0.01, 0.1, 1,10, 100 μM. Based on in vitro cell culture, we use the MTT assay todetect the inhibitory rate of each compound.

The A549 or HL-60 cells were picked up from cell incubator, after washedfor twice using PBS, cells were digested by 0.25% trypsin, and then addmedium to terminate the digestion. After cells were collected usingcentrifuge and re-suspended, count cells under inverted microscope andadd medium to make a density was 5×10⁴ cells/mL. After 100 μL aliquotswere added to each well of 96-well microtiter plates, cells werecultured in 5% incubator for overnight at 37° C., then the differentconcentration compounds were added to each well. After incubation for 48h, MTT solution was added to each well and plates were then incubatedfor 4 h. The MTT tetrazolium was reduced to formazan by living cells.Then the formazan crystals were dissolved though adding DMSO to eachwell. The absorbance was read at 570 nm with a microplate reader.

Part of the test results are as follows:

TABLE 31 Proliferation inhibitory effect of the compounds on A549 cell(% of Control) Compounds Concentration (μM) No. 100 10 1 0.1 0.01 6-1 19.8 20.4 16.9 12.1 13.1 6-23 93.8 93.7 2.5 −1.8 −0.8 6-35 92.7 58.6 1.0−0.8 0.5 6-39 92.6 24.9 19.6 18.8 18.3 6-41 92.0 84.0 13.1 0.7 3.8 6-9398.2 80.3 74.8 39.4 12.1 6-98 93.2 90.1 11.7 −0.7 −2.5 6-99 86.3 83.655.0 0 0  6-113 93.7 75.6 2.6 2.9 9.2  6-114 94.9 82.1 11.5 2.8 10.122-33  90.3 78.7 61.3 −1.1 −1.6 22-93  91.4 73.7 −0.2 −1.8 −2.2 22-10197.5 66.4 19.1 21.4 13.7 22-105 89.8 80.6 49.9 8.8 16 22-120 92.1 86.89.8 0 0.8 22-121 89.5 51.2 9.9 12.4 6.2 22-153 85.2 60.6 14.7 0 3.722-208 91.3 83.2 2.4 −1.2 −1.0 25-105 93.7 78.0 0.9 2.2 3.1 28-105 89.654.9 2.7 5.3 4.1 29-105 91.9 94.2 72.7 −0.5 −0.2 30-104 91.8 78.4 −0.11.1 2.4 30-120 92.0 84.0 −0.7 −0.9 −1.5

TABLE 32 Proliferation inhibitory effect of the compounds on HL-60 cells(% of Control) Compounds Concentration (μM) No. 100 10 1 0.1 0.01 6-1 61.9 63.9 18.8 10.4 11.5 6-3  94.5 72.2 −2.1 −6.3 −7.1 6-10 77.1 78.59.8 16.1 21.8 6-23 90.6 93.2 23.1 10.8 2.3 6-35 89.9 72.3 −1.8 −5.0 −8.36-39 80.8 78.5 31.0 14.7 11.9 6-41 87.9 86.5 7.8 3.9 6.5 6-93 74.8 72.370.7 51.8 0 6-98 95.1 91.7 30.0 10.1 −2.5 6-99 54.8 56.5 60.2 34.2 8.6 6-109 94.4 52.4 2.9 2.2 0.1  6-113 93.1 85.4 9.3 8.8 −3.8  6-114 93.287.5 20.7 10.0 −0.4  6-205 91.9 59.5 5.8 12.6 −3.4 22-24  94.3 82.4 −9.3−16.7 −22.4 22-33  81.2 66.2 54.3 −1.8 −4.9 22-61  89.8 85.7 11.0 7.85.2 22-88  94.1 79.1 −24.6 −32.9 −35.2 22-93  95.4 70.4 6.8 −7.1 −3.622-95  95.4 76.0 32.6 −4.0 0.3 22-98  91.0 77.7 9.5 1.3 −7.3 22-101 64.773.4 48.6 5.5 8.3 22-104 94.0 60.5 −2.1 −7.3 4.1 22-105 53.8 70.4 71.131.7 27.2 22-107 94.4 65.4 −7.0 −9.3 2.8 22-120 61.0 63.1 19.7 20.5 9.622-121 61.2 73.6 47.6 12.5 13 22-122 94.6 57.2 11.7 −1.9 6.3 22-153 65.873.4 59.6 7.3 12.9 22-207 90.5 61.9 0.4 −3.6 7.3 22-208 91.2 91.2 28.9−14.0 −8.0 25-105 88.0 80.2 20.0 4.4 3.1 26-105 88.0 80.2 20.0 4.4 3.128-105 77.2 88.4 13.3 −3.7 4.9 29-105 91.5 95.1 94.7 70.2 11.2 30-10180.7 57.3 −0.3 −14.2 −6.4 30-104 93.3 88.0 65.3 31.6 21.8 30-105 89.085.6 80.6 43.6 −6.8 30-120 95.7 95.9 70.6 39.2 23.6 30-122 82.4 61.318.0 7.4 10.7

Example 23 In Vitro Cell Inhibition Assay Using the Cell CountingKit-8(CCK-8) Method

The human cancer cell lines used for this assay were: non-small celllung cancer A549, NCI-H1650 and NCI-H358, leukemia HL-60, CCRF-CEM andMOLT-4, colon cancer HT-29 and COLO-205, pancreatic cancer BXPC-3,hepatocarcinoma SK-HEP-1, cervical cancer Hela, bladder cancer T24,prostate cancer DU-145 and PC-3, osteosarcoma MG-63, breast cancerMDA-MB-231, intracranial malignant melanoma A375, glioma U251,nasopharyngeal carcinoma CNE.

The concentrations of compounds used for this assay were 0.01, 0.1, 1,10, 100 μM. Based on in vitro cell culture, we use the CCK-8 assay todetect the inhibitory rate of each compound.

The non-small cell lung cancer A549, NCI-H1650 and NCI-H358, coloncancer HT-29 and COLO-205, pancreatic cancer BXPC-3, hepatocarcinomaSK-HEP-1, cervical cancer Hela, bladder cancer T24, prostate cancerDU-145 and PC-3, osteosarcoma MG-63, breast cancer MDA-MB-231,intracranial malignant melanoma A375, glioma U251, nasopharyngealcarcinoma CNE were picked up from cell incubator. After the cell cultureflasks gently shaking, culture fluid was discarded in clean bench. Thenwashed cells for twice using PBS, and add 0.25% trypsin to digest, whenthe cells were turning round, add medium to terminate digestion. Cellswere collected and transferred to centrifuge tube. For the non-adherentcells HL-60, CCRF-CEM and MOLT-4, cell flasks were picked up fromincubator and then transferred to the centrifuge tubes directly. Aftercells were collected using centrifuge at 1000 rpm/min for 5 min, thefluid was discarded. Then cells were washed for one time by PBS, discardfluid. Then add some medium, count cells under inverted microscope usingblood cell counting plate, according the counting number to making thedensity of adherent cell was 1×10⁵ cells/mL, the non-adherent cell was2×10⁵ cells/mL (the volumes of HL-60, CCRF-CEM, MOLT-4 are smaller thannon-adherent cells, these cells added to each well was much morehigher). Add 50 μL aliquots to each well of 96-well plates (the densityof adherent cells was 5000 cells/well, non-adherent cells was 10000cells/well). Blank control, Negative control, blank control withcompounds and positive control wells were grouped, and three replicatewells were used for each data point in the experiments. Then the cellswere cultured in 5% incubator for overnight at 37° C., Then thedifferent concentration compounds were added to each well. Afterincubation for 48 h, according to the manufacturer's instructions, CCK-8reagent (10 μl) was added and incubation was continued for a further 2-4h. The absorbance (A) of each well was read at 450 nm using a platereader.

TABLE 33 Proliferation inhibitory effect of the compounds on A549 cells(% of Control) Compounds Concentration (μM) No. 100 10 1 0.1 0.01 6-2487.36 60.31 31.44 24.27 22.06 6-25 81.32 55.87 17.11 18.59 15.66 6-4799.91 55.57 53.58 49.86 42.56 6-93 98.18 87.64 70.04 19.35 14.77 6-9598.69 97.88 78.63 56.27 39.65 6-100 89.94 57.45 52.15 50.53 43.98 6-11199.83 80.03 53.14 29.42 23.15 6-112 99.26 89.34 76.90 47.20 46.52 6-20183.86 60.23 26.90 19.63 14.31

TABLE 34 Proliferation inhibitory effect of the compounds on HL-60 cells(% of Control) Compounds Concentration (μM) No. 100 10 1 0.1 0.01 6-2495.11 56.72 48.39 17.55 0.00 6-25 84.30 92.02 84.06 42.54 11.52 6-4378.53 73.80 38.45 31.60 23.65 6-45 80.30 52.09 39.89 27.78 0.00 6-4798.51 83.33 41.47 34.70 7.02 6-93 93.71 87.80 82.05 44.96 30.19 6-9596.40 94.99 94.76 43.28 0.00 6-100 97.42 49.85 39.47 26.90 14.24 6-11199.28 95.16 79.31 41.52 13.70 6-112 96.45 97.63 91.55 59.46 48.31 6-20198.14 86.76 75.70 48.61 40.59

TABLE 35 The half maximal inhibitory concentration (IC50) of thecompounds Compound6- Tumor cells Cell culture 93 Gefitinib TaxolNon-small-cell A549 0.715 33.688 83.528 carcinoma NCI-H1650 1.366 16.2600.420 NCI-H358 0.443 1.166 0.278 leukemia HL-60 0.085 34.445 <0.01CCRF-CEM <0.01 12.691 <0.01 MOLT-4 0.167 25.839 <0.01 Colorectal CancerHT-29 0.224 18.310 >100 COLO-205 0.125 6.973 <0.01 Prostate cancerDU-145 0.646 3.371 17.428 PC-3 1.356 77.363 69.019 cervical cancer Hela1.509 35.442 <0.01 bladder cancer T24 0.603 31.346 3.535 nasopharyngealCNE 6.078 43.682 >100 glioma U251 1.616 26.801 >100 pancreatic cancerBXPC-3 0.331 24.011 <0.01 hepatocarcinoma SK-HEP-1 0.489 9.074 0.047breast cancer MDA-MB-231 0.175 >100 2.018 melanoma A375 0.160 35.46355.345 osteosarcoma MG-63 0.196 33.706 <0.01

1-18. (canceled)
 19. A method of treating tumors, comprisingadministering to the subject in need thereof an effective amount of asubstituted diphenylamine compound having the following general formulaI:

wherein: R₁ is selected from the group consisting of H, C₁-C₈alkyl,C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₁-C₈alkylcarbonyl,C₁-C₈haloalkylcarbonyl, C₁-C₈alkoxycarbonyl, C₁-C₈alkylaminocarbonyl,C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl,C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈alkylcarbonyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkylaminothio,C₂-C₈dialkylaminothio, C₂-C₈alkenyl, C₂-C₈alkynyl, C₂-C₈haloalkenyl,C₂-C₈haloalkynyl, aryl C₁-C₈alkyl and CO—X—CO₂R₁₂, in which X isselected from the group consisting of (CHR₁₂)n, CR₁₂═CR₁₃ and C₆H₄,wherein n=1-6; R₂ and R₆ may be the same or different, respectivelyselected from the group consisting of H, halogen, CN, NO₂, COOH,C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₂-C₈alkenyl, C₂-C₈alkynyl,C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl,C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl, and the followinggroups unsubstituted or substituted with 1-5 R₁₄: aryl, arylmethyl,aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl,arylaminocarbonyl or heteroaryloxy, and when the number of thesubstitutes is more than 1, R₁₄ may be the same or different; R₃ and R₅may be the same or different, respectively selected from the groupconsisting of H, halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylamino,C₁-C₈haloalkylamino, C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₂-C₈alkenyl,C₂-C₈alkynyl, C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl,C₁-C₈alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkylcarbonyloxy,C₁-C₈alkoxycarbonyloxy, C₁-C₈alkylaminocarbonyloxy,C₁-C₈alkylsulfonyloxy, C₁-C₈alkoxyC₁-C₈alkoxy,C₁-C₈haloalkoxyC₁-C₈haloalkoxy, C₁-C₈alkoxycarbonylC₁-C₈alkoxy, and thefollowing groups unsubstituted or substituted with 1-5 R₁₄: aryl,arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl,aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the numberof the substitutes is more than 1, R₁₄ may be the same or different; R₄is selected from the group consisting of H, halogen, CN, NO₂, COOH,CO₂Na, CO₂NH₄, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₂-C₈alkenyl, C₂-C₈alkynyl, C₁-C₈alkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈alkoxy,C₁-C₈haloalkoxyC₁-C₈haloalkoxy, SO₂NR₁₂R₁₃, and the following groupsunsubstituted or substituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy,arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl,arylaminocarbonyl or heteroaryloxy, and when the number of thesubstitutes is more than 1, R₁₄ may be the same or different; R₇ is Clor CH₃; R₈ is selected from the group consisting of H, halogen, OH, CN,NO₂, COOH, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkylamino, C₁-C₈haloalkylamino, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, C₃-C₈cycloalkyl,C₂-C₈dialkylamino, C₃-C₈alkenyloxy, C₃-C₈haloalkenyloxy,C₃-C₈alkynyloxy, C₃-C₈haloalkynyloxy, C₁-C₈alkylcarbonyloxy,C₁-C₈alkylcarbonylamino, C₁-C₈alkylsulfonyloxy, C₁-C₈alkoxyC₁-C₈alkoxy,C₁-C₈alkoxycarbonylC₁-C₈alkoxy, and the following groups unsubstitutedor substituted with 1-5 R₁₄: aryloxy, arylamino, arylmethoxy,arylmethylamino, heteroaryloxy or heteroarylamino, and when the numberof the substitutes is more than 1, R₁₄ may be the same or different; R₉is selected from the group consisting of H, halogen, NO₂, CN,C(═O)NR₁₂R₁₃, C(═S)NR₁₂R₁₃, C₁-C₈alkylaminocarbonyl,C₁-C₈alkoxycarbonyl, C₁-C₈haloalkyl and C₁-C₈alkylsulfonyl; R₁₀ isselected from the group consisting of H, halogen, OH, CN, NO₂, COOH,C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkylamino, C₁-C₈haloalkylamino, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, C₂-C₈dialkylamino,C₃-C₈alkenyloxy, C₃-C₈haloalkenyloxy, C₃-C₈alkynyloxy,C₃-C₈haloalkynyloxy, C₁-C₈alkylcarbonyloxy, C₁-C₈alkylcarbonylamino,C₁-C₈alkylsulfonyloxy, C₁-C₈alkoxyC₁-C₈alkoxy andC₁-C₈alkoxycarbonylC₁-C₈alkoxy; R₁₁ is CN or NO₂, R₁₂ and R₁₃ may be thesame or different, respectively selected from the group consisting of H,C₁-C₆alkyl and C₃-C₆cycloalkyl; and R₁₄ is selected from the groupconsisting of halogen, NO₂, CN, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy,C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylcarbonyl,C₁-C₆alkoxycarbonyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₃-C₆alkenyloxy,C₃-C₆haloalkenyloxy, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆alkynyloxy,C₃-C₆haloalkynyloxy, C₁-C₆haloalkylthio, C₁-C₆haloalkylcarbonyl,C₁-C₆alkylamino, C₁-C₆haloalkylamino, C₂-C₈dialkylamino,C₁-C₆alkylcarbonylamino, C₁-C₆haloalkylcarbonylamino,C₁-C₆alkylaminocarbonyl and C₁-C₆haloalkylaminocarbonyl; or saltsthereof.
 20. The method of claim 19, wherein R₇ is Cl, R₉ and R₁₁ areCN, and wherein the compound has the following general formula II:

wherein: R₁ is selected from the group consisting of H, C₁-C₈alkyl,C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₁-C₈alkylcarbonyl,C₁-C₈haloalkylcarbonyl, C₁-C₈alkoxycarbonyl, C₁-C₈alkylaminocarbonyl,C₁-C₈alkylsulfonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxyC₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl,C₂-C₈alkenyl, C₂-C₈alkynyl, C₂-C₈haloalkenyl, C₂-C₈haloalkynyl, arylC₁-C₈alkyl and CO—X—CO₂R₁₂, wherein X is selected from the groupconsisting of (CHR₁₂)n, wherein CR₁₂═CR₁₃ and n=1-6 and C₆H₄; R₂ and R₆may be the same or different, respectively selected from the groupconsisting of H, halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₂-C₈alkenyl, C₂-C₈alkynyl, C₁-C₈alkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, and the following groups unsubstituted orsubstituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy, arylamino,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl orheteroaryloxy, and when the number of the substitutes is more than 1,R₁₄ may be the same or different; R₃ and R₅ may be the same ordifferent, respectively selected from the group consisting of H,halogen, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈haloalkyl,C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylamino, C₁-C₈haloalkylamino,C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₂-C₈alkenyl, C₂-C₈alkynyl,C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl,C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxycarbonylC₁-C₈alkyl,C₁-C₈alkylcarbonyloxy, C₁-C₈alkoxycarbonyloxy,C₁-C₈alkylaminocarbonyloxy, C₁-C₈alkylsulfonyloxy,C₁-C₈alkoxyC₁-C₈alkoxy, C₁-C₈haloalkoxyC₁-C₈haloalkoxy,C₁-C₈alkoxycarbonylC₁-C₈alkoxy, and the following groups unsubstitutedor substituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy, arylamino,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl orheteroaryloxy, and when the number of the substitutes is more than 1,R₁₄ may be the same or different; R₄ is selected from the groupconsisting of H, halogen, CN, NO₂, COOH, CO₂Na, CO₂NH₄, C(═O)NR₁₂R₁₃,C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₂-C₈alkenyl,C₂-C₈alkynyl, C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl,C₁-C₈alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈alkoxy,C₁-C₈haloalkoxyC₁-C₈haloalkoxy, SO₂NR₁₂R₁₃, and the following groupsunsubstituted or substituted with 1-5 R₁₄: aryl, arylmethyl,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl or arylaminocarbonyl,and when the number of the substitutes is more than 1, R₁₄ may be thesame or different; R₈ and R₁₀ may be the same or different, respectivelyselected from the group consisting of H, halogen, OH, CN, NO₂, COOH,C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkylamino, C₁-C₈haloalkylamino, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, C₂-C₈dialkylamino,C₃-C₈alkenyloxy, C₃-C₈haloalkenyloxy, C₃-C₈alkynyloxy,C₃-C₈haloalkynyloxy, C₁-C₈alkylcarbonyloxy, C₁-C₈alkylcarbonylamino,C₁-C₈alkylsulfonyloxy, C₁-C₈alkoxyC₁-C₈alkoxy andC₁-C₈alkoxycarbonylC₁-C₈alkoxy; R₁₂ and R₁₃ may be the same ordifferent, respectively selected from the group consisting of H,C₁-C₆alkyl and C₃-C₆cycloalkyl; R₁₄ is selected from the groupconsisting of halogen, NO₂, CN, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy,C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylcarbonyl,C₁-C₆alkoxycarbonyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₃-C₆alkenyloxy,C₃-C₆haloalkenyloxy, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆alkynyloxy,C₃-C₆haloalkynyloxy, C₁-C₆haloalkylthio, C₁-C₆haloalkylcarbonyl,C₁-C₆alkylamino, C₁-C₆haloalkylamino, C₂-C₈dialkylamino,C₁-C₆alkylcarbonylamino, C₁-C₆haloalkylcarbonylamino,C₁-C₆alkylaminocarbonyl and C₁-C₆haloalkylaminocarbonyl; or the salts ofthe compounds having general formula II.
 21. The method of claim 20,wherein, in the compound having the general formula II, R₁ is selectedfrom the group consisting of H, C₁-C₄alkyl, C₃-C₆cycloalkyl,C₁-C₄haloalkyl, C₁-C₄alkylcarbonyl, C₁-C₄haloalkylcarbonyl,C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkoxyC₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonylC₁-C₄alkyl,C₂-C₄alkenyl, C₂-C₄alkynyl, C₂-C₄haloalkenyl, C₂-C₄haloalkynyl, benzyl,phenethyl and CO—X—CO₂R₁₂, wherein X is selected from the groupconsisting of (CHR₁₂)n, wherein CR₁₂═CR₁₃ and n=1-3, and C₆H₄; R₂ and R₆may be the same or different, respectively selected from the groupconsisting of H, Cl, Br, F, CN, NO₂, COOH, C(═O)NR₁₂R₁₃, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio,C₁-C₄haloalkylthio, C₂-C₄alkenyl, C₂-C₄alkynyl, C₁-C₄alkylsulfonyl,C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkoxycarbonylC₁-C₄alkyl, and the following groups unsubstituted orsubstituted with 1-3 R₁₄: phenoxy, phenylamino, phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, andwhen the number of the substitutes is more than 1, R₁₄ may be the sameor different; R₃ and R₅ may be the same or different, respectivelyselected from the group consisting of H, Cl, Br, F, CN, NO₂, COOH,C(═O)NR₁₂R₁₃, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylamino, C₁-C₄haloalkylamino, C₁-C₄alkylthio,C₁-C₄haloalkylthio, C₂-C₄alkenyl, C₂-C₄alkynyl, C₁-C₄alkylsulfonyl,C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkoxycarbonylC₁-C₄alkyl, and the following groups unsubstituted orsubstituted with 1-3 R₁₄: phenoxy, phenylamino, phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, andwhen the number of the substitutes is more than 1, R₁₄ may be the sameor different; R₄ is selected from the group consisting of H, Cl, Br, F,CN, NO₂, COOH, CO₂Na, CO₂NH₄, C(═O)NR₁₂R₁₃, C₁-C₄alkyl, C₁-C₄haloalkyl,C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₂-C₄alkenyl, C₂-C₄alkynyl,C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl,C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkoxycarbonylC₁-C₄alkyl,C₁-C₄alkoxyC₁-C₄alkoxy, SO₂NHCH₃, SO₂N(CH₃)₂, and the following groupsunsubstituted or substituted with 1-3 R₁₄: phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl or phenylaminocarbonyl, and when thenumber of the substitutes is more than 1, R₁₄ may be the same ordifferent; R₈ and R₁₀ are the same or different, respectively selectedfrom the group consisting of Cl, Br, F, OH, CN, NO₂, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylamino,C₁-C₄haloalkylamino, C₁-C₄alkylthio, C₁-C₄haloalkylthio,C₁-C₄alkylsulfonyl, C₂-C₆dialkylamino, C₃-C₄alkenyloxy,C₃-C₄haloalkenyloxy, C₃-C₄alkynyloxy, C₃-C₄haloalkynyloxy,C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy,C₁-C₄alkoxyC₁-C₄alkoxy and C₁-C₄alkoxycarbonylC₁-C₄alkoxy; R₁₂ and R₁₃are the same or different, respectively selected from the groupconsisting of H and C₁-C₄alkyl; R₁₄ is selected from the groupconsisting of F, Cl, Br, NO₂, CN, C₁-C₄alkyl, C₁-C₄haloalkyl,C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄alkylcarbonyl,C₁-C₄alkoxycarbonyl and C₁-C₄alkylaminocarbonyl; or the salts of thecompounds having general formula II.
 22. The method of claim 21,wherein, in the compound having the general formula II: R₁ is selectedfrom the group consisting of H, CH₃, acetyl, methylsulfonyl, benzyl andphenethyl; R₂ and R₆ are the same or different, respectively selectedfrom the group consisting of H, F, Cl, Br, CN, NO₂, COOH, CONH₂,CONHCH₃, CON(CH₃)₂, CONHCH(CH₃)₂, CONHC(CH₃)₃, CH₃, C₂H₅, CH(CH₃)₂,C(CH₃)₃, ClCH₂, CF₃, CH₃O, C₂H₅O, CF₃O, CF₃CH₂O, CH₃S, CH₃OCO andCH₃OCH₂; R₃ and R₅ are the same or different, respectively selected fromthe group consisting of H, F, Cl, Br, CN, NO₂, COOH, CONH₂, CONHCH₃,CON(CH₃)₂, CONHCH(CH₃)₂, CONHC(CH₃)₃, CH₃, C₂H₅, CH(CH₃)₂, C(CH₃)₃,ClCH₂, CF₃, CH₃O, C₂H₅O, CF₃O, CF₃CH₂O, CH₃S, CH₃OCO and CH₃OCH₂; R₄ isselected from the group consisting of H, F, Cl, Br, CN, NO₂, COOH,CO₂Na, CO₂NH₄, CONH₂, CONHCH₃, CON(CH₃)₂, CONHCH(CH₃)₂, CONHC(CH₃)₃,CF₃, CF₃O, CH₃OCO, C₂H₅OCO, CH₃SO₂, SO₂NHCH₃, SO₂N(CH₃)₂,phenoxycarbonyl, phenylaminocarbonyl, 4-CH₃-phenylaminocarbonyl and4-Cl-phenylaminocarbonyl; R₈ and R₁₀ are the same or different,respectively selected from the group consisting of Cl, F, CH₃O, CF₃O,CF₃CH₂O, CH₃NH, (CH₃)₂N, (C₂H₅)₂N, CF₃CH₂NH, ClCH₂CH₂NH, CH₃S, C₂H₅S,CH₃SO₂, C₂H₅SO₂, (CH₃)₂N, CH₂═CHCH₂O, CH≡CCH₂O, ClC≡CCH₂O, IC≡CCH₂O,CH₃CO₂, CH₃CONH, CH₃OCH₂CH₂O, C₂H₅OCH₂CH₂O, CH₃OC(═O)CH₂O andCH₃OC(═O)CH₂CH₂O; or the salts formed from the compounds of generalformula II with hydrochloric acid, sulfuric acid, nitric acid, hydrogencarbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.
 23. Themethod of claim 22, wherein, in the compound having the general formulaII: R₁ is H; R₂ is selected from the group consisting of H, F, Cl, Br,CH₃, C₂H₅, NO₂ and CN; R₃ is selected from the group consisting of H, F,Cl, Br, CH₃ and CF₃; R₄ is selected from the group consisting of H, F,Cl, Br, CF₃, CF₃O, CH₃OCO, CN, NO₂, COOH, CO₂Na, phenylaminocarbonyl and4-Cl-phenylaminocarbonyl; R₅ is selected from the group consisting of H,Cl, Br, CH₃ and CF₃; R₆ is selected from the group consisting of H, F,Cl, Br, CH₃, C₂H₅, NO₂ and CN; R₈ is selected from the group consistingof Cl, CH₃O, CH₃NH, (CH₃)₂N and (C₂H₅)₂N; R₁₀ is selected from the groupconsisting of Cl, CH₃O and CH₃NH; or the salts formed from the compoundsof general formula II with hydrochloric acid, sulfuric acid, nitricacid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formicacid, acetic acid, trifluoroacetic acid, phenylsulfonic acid,p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid,malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid oroxalic acid.
 24. The method of claim 23, wherein, in the compound havingthe general formula II: R₁, R₃ and R₅ are each a H; R₂ and R₆ are thesame or different, and wherein R₂ and R₆ are each independently selectedfrom the group consisting of H, Cl and Br; R₄ is selected from the groupconsisting of H, Cl, Br, NO₂, CF₃, CF₃O and CH₃OCO; R₈ and R₁₀ are eacha Cl; or the salts formed from the compounds of general formula II withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.
 25. Themethod of claim 24, wherein the compound has one of the followingstructures:


26. The method of claim 19, wherein, in the compound having the generalformula I: R₇ is CH₃; R₁₀ is H; R₁₁ is NO₂; and the structures of thecompound have a general formula III:

wherein: R₁ is selected from the group consisting of H, C₁-C₈alkyl,C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₁-C₈alkylcarbonyl,C₁-C₈haloalkylcarbonyl, C₁-C₈alkoxycarbonyl, C₁-C₈alkylaminocarbonyl,C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl,C₁-C₈alkoxyC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈alkylcarbonyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkylaminothio,C₂-C₈dialkylaminothio and CO—X—CO₂R₁₂, wherein X is selected from thegroup consisting of (CHR₁₂)n, wherein CR₁₂═CR₁₃ and n=1-6, and C₆H₄; R₂and R₆ may be the same or different, respectively selected from thegroup consisting of H, halogen, CN, NO₂, C(═O)NR₁₂R₁₃, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₂-C₈alkenyl,C₂-C₈alkynyl, C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl,C₁-C₈alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, and the following groups unsubstituted orsubstituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy, arylamino,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl orheteroaryloxy, and when the number of the substitutes is more than 1,R₁₄ may be the same or different; R₃ and R₅ may be the same ordifferent, respectively selected from the group consisting of H,halogen, CN, NO₂, C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₁-C₈alkylamino, C₁-C₈haloalkylamino, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₂-C₈alkenyl, C₂-C₈alkynyl, C₁-C₈alkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkylcarbonyloxy,C₁-C₈alkoxycarbonyloxy, C₁-C₈alkylaminocarbonyloxy,C₁-C₈alkylsulfonyloxy, C₁-C₈alkoxyC₁-C₈alkoxy,C₁-C₈haloalkoxyC₁-C₈haloalkoxy, C₁-C₈alkoxycarbonylC₁-C₈alkoxy, and thefollowing groups unsubstituted or substituted with 1-5 R₁₄: aryl,arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl,aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the numberof the substitutes is more than 1, R₁₄ may be the same or different; R₄is selected from the group consisting of H, halogen, CN, NO₂, COOH,C(═O)NR₁₂R₁₃, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₂-C₈alkenyl, C₂-C₈alkynyl, C₁-C₈alkylsulfonyl, C₁-C₈alkylcarbonyl,C₁-C₈alkoxycarbonyl, C₁-C₈alkoxyC₁-C₈alkyl,C₁-C₈alkoxycarbonylC₁-C₈alkyl, C₁-C₈alkoxyC₁-C₈alkoxy,C₁-C₈haloalkoxyC₁-C₈haloalkoxy, and the following groups unsubstitutedor substituted with 1-5 R₁₄: aryl, arylmethyl, aryloxy, arylamino,arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl orheteroaryloxy, and when the number of the substitutes is more than 1,R₁₄ may be the same or different; R₈ is selected from the groupconsisting of H, halogen, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkylamino, C₁-C₈haloalkylamino, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, C₃-C₈cycloalkyl,C₂-C₈dialkylamino, C₃-C₈alkenyloxy, C₃-C₈haloalkenyloxy,C₃-C₈alkynyloxy, C₃-C₈haloalkynyloxy, C₁-C₈alkylcarbonyloxy,C₁-C₈alkylcarbonylamino, C₁-C₈alkylsulfonyloxy, C₁-C₈alkoxyC₁-C₈alkoxy,C₁-C₈alkoxycarbonylC₁-C₈alkoxy, and the following groups unsubstitutedor substituted with 1-5 R₁₄: aryloxy, arylamino, arylmethoxy,arylmethylamino, heteroaryloxy or heteroarylamino, and when the numberof the substitutes is more than 1, R₁₄ may be the same or different; R₉is selected from the group consisting of H, halogen, NO₂, CN,C(═O)NR₁₂R₁₃, C(═S)NR₁₂R₁₃, C₁-C₈alkylaminocarbonyl,C₁-C₈alkoxycarbonyl, C₁-C₈haloalkyl and C₁-C₈alkylsulfonyl; R₁₂ and R₁₃may be the same or different, respectively selected from the groupconsisting of H and C₁-C₆alkyl; R₁₄ is selected from the groupconsisting of halogen, NO₂, CN, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy,C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylcarbonyl,C₁-C₆alkoxycarbonyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₃-C₆alkenyloxy,C₃-C₆haloalkenyloxy, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆alkynyloxy,C₃-C₆haloalkynyloxy, C₁-C₆haloalkylthio, C₁-C₆haloalkylcarbonyl,C₁-C₆alkylamino, C₁-C₆haloalkylamino, C₂-C₈dialkylamino,C₁-C₆alkylcarbonylamino, C₁-C₆haloalkylcarbonylamino,C₁-C₆alkylaminocarbonyl and C₁-C₆haloalkylaminocarbonyl; or the salts ofthe compounds having general formula III.
 27. The method of claim 26,wherein, in the general formula III: R₁ is selected from the groupconsisting of H, C₁-C₄alkyl, C₃-C₆cycloalkyl, C₁-C₄alkylcarbonyl,C₁-C₄haloalkylcarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio,C₁-C₄haloalkylthio, C₁-C₄alkylsulfonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkoxyC₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonylC₁-C₄alkyl,C₁-C₄alkylaminothio, C₂-C₄dialkylaminothio and CO—X—CO₂R₁₂, wherein X isselected from the group consisting of (CHR₁₂)n, wherein CR₁₂═CR₁₃ andn=1-3; and C₆H₄; R₂ and R₆ may be the same or different, respectivelyselected from the group consisting of H, halogen, CN, NO₂, C(═O)NR₁₂R₁₃,C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₂-C₆alkenyl,C₂-C₆alkynyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl,C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkoxycarbonylC₁-C₄alkyl, and the following groups unsubstituted orsubstituted with 1-4 R₁₄: phenoxy, phenylamino, phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, andwhen the number of the substitutes is more than 1, R₁₄ may be the sameor different; R₃ and R₅ may be the same or different, respectivelyselected from the group consisting of H, halogen, CN, NO₂, C(═O)NR₁₂R₁₃,C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylamino, C₁-C₄haloalkylamino, C₁-C₄alkylthio,C₁-C₄haloalkylthio, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₄alkylsulfonyl,C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl and C₁-C₄alkoxyC₁-C₄alkyl; R₄ isselected from the group consisting of H, halogen, CN, NO₂, COOH,C(═O)NR₁₂R₁₃, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄haloalkoxy, C₂-C₆alkenyl,C₂-C₆alkynyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl,C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkoxycarbonylC₁-C₄alkyl, C₁-C₄alkoxyC₁-C₄alkoxy, and the followinggroups unsubstituted or substituted with 1-4 R₁₄: phenoxy, phenylamino,phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl orpyridyloxy, and when the number of the substitutes is more than 1, R₁₄may be the same or different; R₈ is selected from the group consistingof H, halogen, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylamino,C₁-C₄haloalkylamino, C₁-C₄alkylthio, C₁-C₄haloalkylthio,C₁-C₄alkylsulfonyl, C₂-C₄dialkylamino, C₃-C₄alkenyloxy,C₃-C₄haloalkenyloxy, C₃-C₆alkynyloxy, C₁-C₄alkylcarbonyloxy,C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxyC₁-C₄alkoxy,C₁-C₄alkoxycarbonylC₁-C₄alkoxy, and the following groups unsubstitutedor substituted with 1-3 R₁₄: phenoxy, phenylamino, benzyloxy,benzylamino, pyridyloxy or pyridylamino, and when the number of thesubstitutes is more than 1, R₁₄ may be the same or different; R₉ isselected from the group consisting of Cl, Br, F, NO₂, CN, C(═O)NR₁₂R₁₃,C(═S)NR₁₂R₁₃, CO₂CH₃, CF₃ and CH₃SO₂; R₁₂ and R₁₃ may be the same ordifferent, respectively selected from the group consisting of H andC₁-C₃alkyl; R₁₄ is selected from the group consisting of halogen, NO₂,CN, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy,C₁-C₃alkylthio, C₁-C₃alkylcarbonyl, C₁-C₃alkoxycarbonyl,C₁-C₃alkylamino, C₂-C₄dialkylamino, C₁-C₃alkylcarbonylamino andC₁-C₃alkylaminocarbonyl; or the salts of the compounds having generalformula III.
 28. The method of claim 27, wherein, in the compound ofgeneral formula III: R₁ is selected from the group consisting of H, CH₃,C₂H₅, cyclopropyl, formyl, acetyl, COCF₃, CO₂CH₃, CO₂C₂H₅, SCCl₃,SO₂CH₃, SO₂C₂H₅, CH₂OCH₃, CH₂OC₂H₅, CH₂CH₂OCH₃, COCH₂OCH₃, CH₂COOCH₃,SNHCH₃, SN(CH₃)₂, COCH₂CO₂H, COCH₂CO₂CH₃, COCH₂CH₂CO₂H, COCH₂CH₂CO₂CH₃,COCHCH₃CO₂H, COCHCH₃CO₂CH₃, COC₆H₄CO₂H, COC₆H₄CO₂CH₃, COCH═CHCO₂H andCOCH═CHCO₂CH₃; R₂ and R₆ may be the same or different, respectivelyselected from the group consisting of H, Cl, Br, F, CN, NO₂, C(═O)NH₂,C(═O)NHCH₃, C(═O)N(CH₃)₂, CH₃, C₂H₅, CF₃, OCH₃, OC₂H₅, OCF₃, SO₂CH₃,SO₂C₂H₅, COCH₃, CO₂CH₃, CO₂C₂H₅, phenoxy, phenylamino, phenoxycarbonyland phenylaminocarbonyl; R₃ and R₅ may be the same or different,respectively selected from the group consisting of H, Cl, Br, F, CN,NO₂, C(═O)NH₂, CH₃, CF₃, OCH₃, OCF₃, NHCH₃, SCH₃, SO₂CH₃, SO₂C₂H₅,COCH₃, CO₂CH₃, CO₂C₂H₅ and CH₂OCH₃; R₄ is selected from the groupconsisting of H, Cl, Br, F, CN, NO₂, CO₂H, C(═O)NH₂, C(═O)NHCH₃,C(═O)N(CH₃)₂, CH₃, CF₃, CF(CF₃)₂, OCF₃, OCH₂CF₃, OCF₂CHFCF₃, SO₂CH₃,SO₂C₂H₅, COCH₃, CO₂CH₃, CO₂C₂H₅, phenoxy, phenylamino, phenylcarbonyl,benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl, pyridyloxy and3-chloro-5-(trifluoromethyl)pyridin-2-yloxy; R₈ is selected from thegroup consisting of H, Cl, Br, F, C₁-C₃alkoxy, C₁-C₃haloalkoxy,C₁-C₃alkylamino, C₁-C₃haloalkylamino, SCH₃, SC₂H₅, N(CH₃)₂, N(C₂H₅)₂,OCH₂OCH₃, phenoxy, phenylamino, benzyloxy, benzylamino, 4-chlorophenoxy,4-chlorophenylamino, 2-chloro-4-(trifluoromethyl)phenoxy,2-chloro-4-(trifluoromethyl)phenylamino,3-chloro-5-(trifluoromethyl)pyridin-2-yloxy and3-chloro-5-(trifluoromethyl)pyridin-2-ylamino; R₉ is NO₂; or the saltsformed from the compounds of general formula III with hydrochloric acid,sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid,phosphoric acid, formic acid, acetic acid, trifluoroacetic acid,phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid,benzoic acid, citric acid, malic acid, tartaric acid, maleic acid,succinic acid, ascorbic acid or oxalic acid.
 29. The method of claim 28,wherein, in the compound of general formula III: R₁ is selected from thegroup consisting of H and CH₃; R₂ and R₆ may be the same or different,respectively selected from the group consisting of H, Cl, Br, F, CN,NO₂, C(═O)NH₂, C(═O)NHCH₃, C(═O)N(CH₃)₂, CH₃, CF₃, CO₂CH₃ andphenoxycarbonyl; R₃ and R₅ may be the same or different, respectivelyselected from the group consisting of H, Cl, Br, F, CN, NO₂, CH₃, CF₃and OCH₃; R₄ is selected from the group consisting of H, Cl, Br, F, CN,NO₂, CO₂H, C(═O)NH₂, C(═O)NHCH₃, CH₃, CF₃, OCF₂CHFCF₃, CO₂CH₃ and3-chloro-5-(trifluoromethyl)pyridin-2-yloxy; R₈ is selected from thegroup consisting of H, Cl, OCH₃, OCH₂CF₃, NHCH₃, SCH₃ and N(CH₃)₂; R₉ isNO₂; or the salts formed from the compounds of general formula III withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.
 30. Themethod of claim 29, wherein, in the compound of general formula III: R₁,R₃ and R₅ are H; R₂ is selected from the group consisting of Cl and F;R₄ is selected from the group consisting of H, Cl, CN, NO₂ and CF₃; R₆is selected from the group consisting of F, Cl, CN and NO₂; R₈ isselected from the group consisting of H, Cl and OCH₂CF₃; R₉ is NO₂; orthe salts formed from the compounds of general formula III withhydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid,carbonic acid, phosphoric acid, formic acid, acetic acid,trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid,methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaricacid, maleic acid, succinic acid, ascorbic acid or oxalic acid.
 31. Themethod of claim 30, wherein the compound has one of the followingstructures:


32. The method of claim 19, wherein the substituted diphenylaminecompound or salt thereof as an active ingredient is administered throughoral medication, a parenteral route or implantable medication pump. 33.The method of claim 32, wherein the active ingredient is one or moresubstituted diphenylamine compounds.
 34. The method of claim 33, whereinthe substituted diphenylamine compound and salt thereof is administeredin the form of tablets, pills, capsule, granule, syrup, injection orfreeze-dried powder injection.
 35. The method of claim 32, wherein thetumor is colon cancer, liver cancer, lymph cancer, lung cancer,esophageal cancer, breast cancer, central nervous system cancer,melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia,prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer,osteosarcoma, nasopharynx cancer or stomach cancer.
 36. A method ofcuring, preventing or alleviating cancer, comprising: administering to asubject in need thereof an effective amount of the substituteddiphenylamine compound of claim 1 or salt thereof.
 37. A method oftreating tumors comprising: administering to the subject in need thereofan effective amount of a substituted diphenylamine compound of thefollowing structure:


38. A method of treating a tumor comprising administering an effectiveamount of a substituted diphenylamine compound of claim 1 having generalformula I or salt thereof, as an active ingredient, in combination witha common drug carrier used in combination with the active ingredient.39. A pharmaceutical composition for treating a tumor, comprising aneffective amount of a substituted diphenylamine compound of claim 1having general formula I or salt thereof, as an active ingredient, incombination with a common drug carrier used in combination with theactive ingredient.